Denise Huxtable begins her sophomore year at Hillman and moves into Gilbert Hall. She meets her roommate, Jaleesa Vinson, a 26-year-old divorcée who is the subject of much rumor and innuendo. Denise feels uneasy around Jaleesa and asks Stevie Rallen, the resident director, to find her a new room. Denise decides to try harder to get along with Jaleesa, but Jaleesa is offended that Denise has gone behind her back. They get into an argument, and Denise moves in with wealthy Whitley Gilbert (for whose family the dormitory is named). Whitley drives Denise insane with her idiosyncrasies and generally self-absorbed behavior. Denise apologizes to Jaleesa and asks for another chance, and Jaleesa agrees to stop being so defensive. Meanwhile, overeager freshman Dwayne Wayne hits on every woman in sight.

Denise is apprehensive about a visit from her grandfather, as she fears that she cannot live up to his expectations. Jaleesa and Maggie ask Denise to take part in a traditional homecoming prank by stealing the head of the rival mascot's bear costume. (They would be the first women in Hillman history to accomplish this.) Denise initially turns them down because she does not want to disappoint her grandfather. She does not realize that Russell tried to steal the bear head in 1935, but was bested by a friend. He is still bitter about this, and bets his friend that he can pull off the feat. Denise decides to help her roommates after Whitley angers her by belittling the prank as ""foolishness."" Russell and the girls separately seek the assistance of Hillman mascot Dwayne, who distracts the guys assigned to guard the mascot. Denise and her grandfather simultaneously try to steal the mascot head; they realize they have misjudged each other. The girls leave the head in Whitley's bed as revenge

Denise shows potential as a sprinter during P.E. class, and the track coach asks her to come out for the team. Her father is thrilled to have another Huxtable competing for Hillman, as he and his father both ran for the school. Denise enjoys the attention she receives from her friends and other students, but cannot handle the grueling practices. She considers quitting until a star runner informs her that she is not the only one who hates practice; in fact, the entire team feels this way. Maggie desperately tries to track down an economics book that she needs for a term paper.

Dwayne annoys a graduate student with his stupid pick-up lines. She predicts that Dwayne would freak out if a woman actually responded to his advances, and decides to invite him to her apartment. Jaleesa takes bets from the entire dorm on Dwayne's possible reaction. Denise feels that Dwayne does not deserve this treatment, and warns him that he is being set up. Ron persuades Dwayne to go to Peggy's apartment and win her over with his charm. Denise and Walter (Dwayne's resident director and P.E. teacher) try to convince Dwayne to be himself around women. Peggy realizes that Dwayne is a good guy and cannot follow through with the bet.

Jaleesa fills in as resident director after Stevie leaves the university to get married (to Professor Walcott?). The students attend a lecture by Lettie Bostic, a renowned world traveler. Lettie dropped out of Hillman and moved to Paris, where she kept company with Picasso and other artistic icons and even worked as a spy during World War II. She confesses that she still regrets quitting school, so the dean offers to give her credit for ""life experience"" if she takes over as Gilbert's resident director. During a dorm meeting, Lettie immediately rubs the girls the wrong way with her blunt comments. Jaleesa, who is bitter about losing her leadership position, organizes a revolt in the hopes of driving Lettie away. Lettie covers for the girls when they break a television set, and both sides agree to be less abrasive.

Maggie and Denise plan a summer vacation in Greece. Denise realizes that her parents may not allow her to go, let alone agree to finance the trip, because of her terrible grades. She plans to soften up her mother during a weekend visit. Clair arrives at Hillman on her own after Denise fails to pick her up on time, and Lettie unwittingly fills her in on the trip. Clair refuses to let Denise go to Greece. She and Cliff have decided to make Denise get a summer job, in the hopes that she might take her education seriously if she helps finance it. Denise believes that her parents consider her worthless, but Clair eases her mind. Jaleesa decides to join Maggie in Greece. Whitley fears that she will have to spend her birthday alone after Millie bails on her because of plans with Ron. She does not realize that Millie and Ron have thrown together a surprise party.

As the school year begins, Dwayne faces the prospect of taking a calculus class from Col. Taylor, a tough professor nicknamed ""Dr. War."" He fears that Col. Taylor could expose his academic success as a fluke and destroy his dreams of becoming an engineer, so he asks Walter to help him get into another section. Walter believes that Dwayne could thrive under Col. Taylor's tutelage, and asks the professor to talk to him. Col. Taylor manages to change Dwayne's mind and convince him to enroll in his class. Whitley meets new roommate Kim Reese, a headstrong freshman who plans to become a doctor. Whitley hopes to intimidate Kim and drive her to another room, but finds it impossible to break her. Jaleesa's cheerful freshman roommate, Freddie Brooks, develops a massive crush on Dwayne.

Kim becomes overwhelmed by her hectic schedule, as she tries to balance pre-med courses with work and extracurricular activities. She also obsesses over her grades, suffering from nightmares about getting too many B's to make it into medical school. She buys a datebook and tries to plan every moment of her day, ignoring her friends' warnings that her lack of sleep could endanger her health. Kim finally agrees to cut back on her activities after fainting in the Pit. Mr. Gaines quarrels with his wife over the presence of their grown son, whom he wants to throw out of the house. Mr. Gaines crashes at Col. Taylor's place after Velma kicks him out, and quickly wears out his welcome.

Dwayne and Whitley run into each other on a flight back to school. Whitley finds that Dwayne has changed over the summer, as he is dressed in an expensive suit and seems to have matured during his successful internship at Kinishewa. Dwayne comforts Whitley when the plane experiences turbulence. Whitley kisses Dwayne in front of her entire dorm, prompting much teasing from her friends. Each insists that they are only friends. Whitley goes to Dwayne's apartment to see him, but is turned off when she finds him dancing like an idiot at a party. The residents of Gilbert Hall struggle to adjust to the fact that the dorm is now coed. Walter is the resident director, with Jaleesa as resident assistant.

Dwayne's old friend Milt comes for a visit. He believes that Hillman is holding Dwayne back, and encourages him to transfer to the University of Pennsylvania. Milt also recommends that Dwayne distance himself from ""dead weight"" like Ron. Dwayne considers his friend's words, until a talk with Whitley helps remind him of Ron's good qualities and the feeling of family that Hillman holds for its students. He defends the school's academic reputation to Milt. Col. Taylor and Mr. Gaines attend a reunion for U.S. servicemen. Col. Taylor tries to start a romance with a nurse he knew in Vietnam, only to discover that she is a complete mess.

Whitley plays matchmaker for Dwayne and a beautiful coed in the hopes of convincing him to move on. However, she becomes extremely jealous and tries to sabotage the couple's date. Dwayne and Whitley try to establish some ground rules in an attempt to save their friendship. Walter angers Jaleesa by claiming that women cannot play poker. He bets that she cannot teach Freddie how to play, while Jaleesa challenges him to turn novice Kobie into an accomplished player. Neither apprentice picks up the game, but Jaleesa literally beats the pants off of Walter.