In New York City, aspiring novelist Larry Hubbard works as a greeting card writer and is promoted after impressing his supervisor with a new sympathy card. Feeling optimistic, Larry arrives home to find his girl friend, Danielle, in bed with another man. He is slow to realize that the relationship is over and Danielle wants him to move out immediately. While wandering the streets wondering where he is going to live, Larry encounters an acquaintance, Jack Bedwood, who is accompanied by his wife, Verna, and his lover, Frieda. A self-assured philanderer, Jack admits that he also had an affair with Danielle. On a park bench, Larry meets an “experienced lonely guy,” Warren Evans, whose latest girl friend just left him. Larry takes Warren’s advice and buys ferns to keep him company in his new apartment. Hoping for a date, Larry finds the one name listed in his address book, Carol Zall, and telephones her at the bank where she works. He is unaware that the bank is in the middle of a hold-up and Carol is being held hostage. The robber, who answers the phone, informs Larry that Carol would “love” to speak with him, but she is “tied-up” at the moment. Encouraged, Larry leaves a message and waits by the phone, only to be disappointed when she does not return his call. He practices card tricks, telling Warren Evans that woman are impressed by magicians. He also flirts with fellow donors at the blood bank, but is unable to meet anyone. Warren hosts a party, but Larry is the only guest among an apartment filled with cardboard cutouts of famous people that Warren purchased at the Lonely Guy Store. Taking Warren’s advice again, Larry searches for a suitable dog, but abandons the idea as women fawn over the cute canine and ignore him. Next, he pretends to be an athletic jogger. Spraying on fake sweat after a fifty-yard run, Larry approaches a pretty woman in a café, but she recognizes the prank and asks how long he has been “a lonely guy.” Nevertheless, she is sympathetic to his predicament and writes her phone number on a napkin. The next morning, Larry discovers he accidently smudged the numbers and her name, and spends the entire day trying to telephone various combinations. When Larry arrives at a restaurant and announces to the maitre d’ that he is dining alone, all the customers stop eating and stare at him. Followed by a spotlight, Larry is seated at a center table and pretends to be a restaurant critic to convince everyone he is alone on purpose. The pretty woman from the café is also there, and Larry is relieved to finally learn her name is Iris. Once again, she gives him her phone number, writing it on his restaurant tab. After she departs, however, the maitre d’ burns the check, telling Larry there is no charge for an esteemed critic. Larry proceeds to call every Iris in the phone book and returns to the café where they met, but does not find her. Warren Evans leaves a telephone message about killing himself, and Larry rushes to the Manhattan Bridge, a well-known hangout for suicidal lonely guys. On the way, he spots Iris on another subway train and borrows a gang’s graffiti spray-paint to instruct her to meet him at the bridge. Confronted by both Larry and Iris and the thought they might introduce him to a woman one day, Warren decides not to jump. During their first date, Iris tells Larry about the six ex-husbands who left her. She recalls one of them abandoned her at a restaurant when she went to the restroom, so Larry proves his devotion by accompanying her to the ladies’ room and occupying the adjacent stall. That night, Iris is afraid to have sex with Larry because he is “so right” for her and believes she would never survive if he ever left her. Therefore, Iris ends the relationship before becoming further attached. In the wake of the breakup, Larry is fired from his job for submitting a series of depressing greeting cards and concentrates on finishing his novel. While struggling to convey love scenes, he decides instead to write A Guide for the Lonely Guy. The book is an instant bestseller, and Larry becomes an “ex-lonely guy,” appearing on television talk shows, magazine covers and in gossip columns, which report on his love affair with celebrity Loni Anderson. Although surrounded by attention from women, Larry is preoccupied with thoughts of Iris. He invites her to a party, and the two spend the night together. Despite having a wonderful time, Iris remains afraid Larry will eventually abandon her, and she leaves him again. In an effort to forget, Larry takes a cruise, but during the voyage, he learns Iris is on the same ship and they meet at the Masquerade Ball. Playboy Jack Bedwood is also aboard and interrupts their conversation, enticing Iris to dance. Yielding to her pattern of choosing unsuitable husbands, Iris makes plans to marry Jack, and Larry returns to watering ferns in his apartment and spending time with Warren. While watching a television program about an elderly lonely guy, who dies surrounded by cardboard cutouts, Larry suddenly realizes he must stop Iris’s wedding, scheduled for that afternoon. With traffic at a standstill and trains running behind, Larry runs to the church. However, he is too late as Iris and Jack depart as man and wife. The couple celebrates their honeymoon on the ship where they met, but Iris is preoccupied with thoughts of Larry. On the Manhattan Bridge, Larry prepares to commit suicide, and Warren arrives to tell him that he has met someone, so there is hope. Suddenly, Iris, who has jumped from a higher level of the bridge, falls into Larry's arms. They declare their love and join Warren and his new girl friend, noted psychologist Dr. Joyce Brothers, on a date.