Adaptation of Armistead Maupin's third novel about the lives of the residents of 28 Barbary Lane in San Francisco. Set in 1981, four years after "More Tales of the City" concluded, this installment finds Michael Tolliver pursuing cops, cowboys and a closeted movie star, Cage Tyler, while getting over his breakup with Dr. Jon Fielding, now working on a cruise ship. Mary Ann Singleton debates marrying her boyfriend Brian while searching for the big story that will make her a real reporter. Meanwhile, society columnist Prue Giroux falls for a homeless man with a sinister past, socialite DeDe Halcyon returns from the dead after the Jonestown Massacre, and landlady Anna Madrigal meets a new beau with the help of her brothel-running mother.Landlady Anna Madrigal is stunned by her mother's sudden arrival. Mother Mucca is in town to take care of personal business and meets a man from her past, Royal Reichenbach. When Mother Mucca introduces Anna to Royal, they find themselves in a rivalry over him. Madrigal's tenants have their own stories from the past to unravel. Michael Tolliver is working at a nursery and exploring his sexuality full tilt. Michael's friend and neighbor Mary Ann Singleton is longing to be a serious reporter, but not given a chance by her station manager, she is forced to work as a daytime host of the "Bargain Matinee" show.
Mary Ann's late boss' widow, socialite Frannie Halcyon, is tormented by her daughter DeDe's apparent demise in the Jonestown Massacre. Living on mai tais and sleeping pills, she refues to accept that DeDe and her children, Anna and Edgar were killed. She seeks advice from psychics to help her find her missing daughter. When a fortune-teller convinces her that DeDe is indeed alive, she asks for the support of society columnist Prue Giroux to make the story public. When Prue refuses to get involved, Frannie calls Mary Ann to share her secret. Since Mary Ann is always searching for a good story, she is eager to meet in hopes of finally getting a break on the evening news.
Meanwhile, Prue meets a mysterious homeless man, Luke, in Golden Gate Park. Immediately drawn to his intense charm, she falls madly in love with him. Little does she know that she's asking for trouble when she attempts to bring him back to society with the help of flamboyant celebrity priest Father Paddy Star. Luke's past is far more sinister than Prue could ever imagine. Then it's revealed that DeDe has spent three years in Cuba with her lover D'orothea after escaping the massacre in Guyana. She ends up in a camp for gay Cuban refugees in Fort Chafee, Arkansas, and finally calls her mother Frannie in San Francisco to tell her that she wants to come home. Through DeDe's unexpected reappearance and a twist of fate, the various storylines eventually intertwine in the midst of an unpredictable adventure.