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In the late 1980s and early 1990s, friends in Manhattan’s East Village struggle to build the lives of their dreams. Pennilessness, drug abuse, HIV/AIDS, social tension, and political unrest, among other hardships, challenge the group physically and emotionally. Facing the problems head on, they make personal self-discoveries and find what really matters most in life.

Collins, a gay man, is attacked & mugged as he heads to his apartment

Collins & Angel learn that they are both HIV positive. It is revealed that Roger also has HIV, which he contracted from his last girlfriend, who died by suicide after learning of her diagnosis, causing Roger to fall into depression. 

Angel shares the money she made and the amusing story of how she killed a dog to earn it. ("Today 4 U")

Benny arrives to the apartment and speaks of Maureen's upcoming protest against his plans to evict the homeless from a lot where he is hoping to build a cyber arts studio.

Mark then joins Collins and Angel to film their HIV support group meeting ("Life Support"). Roger reflects on his fear of dying an undignified death from AIDS, while the Life Support group echoes his thoughts ("Will I").

Collins, Mark, and Angel protect a homeless woman from police harassment using Mark's camera, but she chastises them because she believes they only did it so Mark can make a name for himself from her situation ("On the Street").

Mimi and Roger each discover that the other is HIV-positive and hesitantly decide to move forward with their relationship ("I Should Tell You").

Maureen removes her jean pants enough to reveal her buttocks and slaps it.

Mimi, Roger’s girlfriend, goes to her drug dealer for a fix ("Happy New Year B"). Roger and Mimi's relationship is strained by Mimi's escalating heroin usage.

At a hospital, Collins supports Angel whose health is declining due to AIDS ("Without You").

A dance is performed representing all the couples' sex lives ("Contact"). At the climax of the number Angel suddenly dies. At the funeral, the friends briefly come together to share their memories, with Collins being the last to reminisce ("I'll Cover You [Reprise]").

Mimi’s health declines and she agrees to go to a rehab. 

Collins is forcibly removed from the church for being unable to pay for Angel's funeral.

Maureen and Joanne abruptly enter the apartment carrying Mimi, who had been homeless and is now weak and close to death. She begins to fade, telling Roger that she loves him ("Finale"). Roger tells her to hold on as he plays her the song he wrote for her, revealing the depth of his feelings for her ("Your Eyes"). Mimi appears to die, but abruptly awakens, claiming to have been heading into a white light before a vision of Angel appeared, telling her to go back and stay with Roger.