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When asked over the phone for his name, he frequently responds, "Fred Sanford. That's S-A-N-F-O-R-D period" or "Fred G. Sanford. The 'G' is for...", with "G" standing for a word applicable to the situation. Some instances have included "gonna cry", "genius", "gee", "grandpa", "gompergoo" and as Lamont himself once said in the episode, "The Reverend Sanford", "Glory glory, Hallelujah". It is never revealed what the "G" actually stands for in his name, though it is possible that it could mean "Glen", the middle name of Foxx's real-life brother, or possible that it could mean "Grady", due to the middle name of Lamont Grady Sanford, known in an early episode where Lamont almost got married. Another trademark involves Fred becoming riled by somebody, assuming a fight stance, and wildly swinging his fists in multiple directions; often he would pose the question, "How would you like one across yo' lips?" or, with fist raised, "How would you like one of these where you sneeze?".

He also frequently attempts to avoid any kind of labor, especially when asked by Lamont, by referring to his arthritis (which he pronounced "arthur-itis") while holding up a deliberately gnarled fist. When Lamont asks him what he does all day while he is out on the truck, Fred often says, "Coordinate."

Fred spends much of his free time watching television (having an affinity for daikaiju films such as the Godzilla series) and drinking a favorite cheap wine called Ripple. Ripple is a frequent joke as well, as often Fred comes up with weird combinations of Ripple and other alcoholic beverages, like with champagne ("Champipple"), or cranberry juice ("Cripple"), or a French wine called Beaujolais ("Beaujolipple"). He even once developed a taste for Sangria wine, calling it "Flapple" because he felt it tasted like flat Ripple.

Another recurring joke is his poor vision; whenever he gets ready to make a phone call, he opens a drawer under the phone and pulls out several pairs of glasses (to help him see the phone dial) and tries each one on until he finds one that seems to help, though the pair he picks usually does not improve his vision, anyway. He, along with Lamont, also often kept valuables or stashes of cash in a secret drawer in that same chest of drawers, which would open after a series of knocks on the dresser and/or foot stamps on the floor. (While Lamont usually pounded on the top of the chest three times, then once on the side, Fred often did various weird combinations to open it.)

In what would become the character's best known trademark, when something would alarm him, or when things did not go the way he wanted them, Fred would inevitably have a simulated heart attack, accentuated by clutching his chest and crying out to his late wife, "Oh, this is the big one! You hear that, Elizabeth?! I'm coming to join you, honey!" However, in real life, Foxx actually died of a heart attack while rehearsing for the role of Alfonso Royal in the CBS sitcom, Royal Family. When Lena Horne guested on the program, and Lamont saw her, he reacted the same way: "I think I'm havin' one, pop! My first one and it's a big one… you hear that, mom? Your little boy's comin' to join ya… with a mustache!"

Fred often clashed with Elizabeth's older sister, Lamont's aunt Esther Anderson (LaWanda Page). Aunt Esther and her family had opposed Fred marrying Elizabeth from the very beginning, and Fred and Esther continue their mutual animosity unabated, despite the best efforts of Lamont. Fred makes a habit of teasing Esther because he thinks she is unattractive (Fred once told Esther, "I could stick your face in some dough and make gorilla cookies!"). For her own part, Esther took no sass from Fred, often referring to him as a "heathen", "sucka", and "fish-eyed fool", and she often tried to use her Bible to change Fred's ways (both figuratively and literally; Esther both quoted from the Bible and also often tried to whack Fred with the heavy purse that she carried it in). Much of the show's comedy came from the interplay between opinionated Fred and his strong-willed sister-in-law.

Prejudices

Throughout the series' run, Fred was often portrayed as being prejudiced himself. He often insults his Puerto Rican neighbor Julio in various ways, including deprecating his culture and making fun of his accent. After Julio greeted him with "Buenos dias, Mr. Sanford," Fred mocked the expression by responding, "And beans and disease to you, too." He also insults Lamont's Japanese friend, Ah Chew, calling him "Choo Choo" and threatening to "really close your eyes" when Ah Chew attempted to hug him. He states at one point that "ain't nothin' on earth uglier than a 90-year-old white woman." His ignorance towards other cultures causes him a severe embarrassment when a Japanese family, interested in buying Fred's land, invites him and Lamont to dinner. The grown daughter sees him eating what he mistakenly thinks are grapes, and smiles "Oh, Mr. Sanford! I am so happy! You like the fish eyes!" Perhaps the biggest affront to Fred's sensibilities came when he discovered his beloved younger sister—whom he had raised himself after their parents died—had married a white man (who was also extremely fond of hugging, further earning him Fred's ire). Sometimes even being African-American did not help with Fred, as he was very untrusting of Lamont's friend Rollo (Nathaniel Taylor) often referring to him as a convict because of his style, as well as often deriding whether or not fellow African-Americans have high end jobs (like managers) and not "typical" black-person jobs (janitors, car wash employees, etc.), and even not placing people like a judge on the same level. (Fred: "That's the problem. A black man doesn't have a chance here!" Judge: "I'm black!" Fred: "Well, you the judge. That don't count.") Despite this, one of Fred's closest friends during the series was a Jewish man named Goldstein; at one point, Fred dons a yarmulke in order to go over to Goldstein's house and eat chicken soup. During a later episode, Fred attempts to trace his family tree and is mistakenly led to believe he has Jewish ancestry.

Relationships with women

Fred was depicted as having an eye for the ladies. In addition to his longtime girlfriend Donna, Fred attempted to hook up with topless waitress "Fast" Fanny, a traveling saleswoman named Carol, and even celebrities such as Lena Horne and Della Reese. Fred wasted no opportunities to flirt with attractive women regardless of location or situation, such as nurses (at the clinic where he got screened for tuberculosis, Fred remarked that a nurse had "TB… Terrific Body!"; similarly, when an attractive nurse came into his hospital room offering a back rub to calm him down, Fred immediately began primping once she left the room), stewardesses (a running gag in the episode where Fred takes his first plane trip involved his constant leering at the attractive stewardess whenever she walked away), and receptionists (when the receptionist at the dental clinic said "I just need to have you answer a few questions," Fred came back with "And may I ask you one or two questions as well.") Lamont once remarked to Fred, "You're just a dirty old man!"; Fred immediately replied, "And I'm gonna be one until I'm a dead old man." Sometimes, it could come back to bite him, as a woman he once wooed over a few too many drinks came looking for him during the episode, "Will the Real Fred Sanford Please Do Something" (one of the episodes filmed in Foxx's absence), to take him up on a wedding proposal, and is stuck thinking every person in the room is Fred at one point, starting with Grady and ending with the Caucasian Hoppy (who was rather amused by this), before finally being taken away by Hoppy and Smitty. (Though Lamont, once it was all over, said he was going to have a talk with Fred about this when he gets back, it was completely forgotten.)

Friendships

Fred has had many friends in the neighborhood, starting with Melvin (Slappy White), and a lot of others, like Leroy, Skillet, etc. from the pool hall. However, his two best friends are Grady Wilson (Whitman Mayo) and Bubba Bexley (Don Bexley). Even though Fred thinks the two are dim witted, he knows that they are more than reliable and can always lend him a helping hand.