Peter is a self-conscious employee at a publishing firm who attends a party. There he meets Rita, a seemingly carefree part-time bartender who hopes to be a graphic designer. The two realize a mutual attraction and begin dating. Over time, Rita reveals her fears about the world, and her hesitancy to invest in joy or dreams when she expects bad things are more likely to happen than good. Despite this, she falls in love with Peter and agrees to marry him.

Some time later, the two marry. At their wedding reception, they encounter an unknown Old Man who was passing by and wanted to wish the couple good luck. The Old Man asks to kiss the bride before he leaves and Rita agrees, charmed. As they kiss, Rita and the Old Man magically exchange bodies. Confused and disoriented, Rita wanders away, now inhabiting an elderly male form, while "Rita" and Peter embark on a honeymoon in Jamaica. During the trip, Peter is confused by his wife's new personality and inability to remember basic details of her own life. When they return home, "Rita" seems back to her old self and kisses Peter. After the kiss, Peter realizes this isn't his wife and concludes the impostor read Rita's diary to better masquerade as her. Panicked, he demands her return then leaves the apartment.

At the bar where Rita worked, Peter sees the Old Man from the wedding reception. They talk and Peter realizes this is the real Rita, who has been living as the Old Man (whose name is Julius). They hope to make another body swap, but discover the Old Man has fled to stay with Rita's parents the Boyles, telling them the marriage is in turmoil and separation is needed. Peter meets Leah, Julius's daughter, and learns the Old Man is a retired widower who has terminal cancer, with maybe a year left to live. As they consider what to do, Peter and Rita live together as a couple again. Rita now appreciates life more deeply, while Peter realizes he loves her despite the shell she inhabits changing how they relate physically.

Peter and Rita finally confront Julius, but the Old Man himself isn't sure how to cause the body swap. He came upon their wedding by chance and envied the bride's youth due to his fear of dying. Rita realizes that during their kiss, she had felt envy for the Old Man as well, wishing she could be someone who had already survived into old age despite any obstacles. As the two realize they no longer have the fears they felt that day, Rita and Julius exchange souls again. Julius takes his leave as Rita and Peter reunite.

Critic Frank Rich wrote: "...this play can be taken as an indirect treatment of [AIDS]. The epidemic is to Mr. Lucas what Babi Yar was to D. M. Thomas, and Peter's fidelity to his true love's soul is transparent.^[2] Critic James Hebert wrote: "When it premiered in 1990 it was widely presumed to be an oblique response to the ravages of AIDS. Long removed from that time, it becomes a broader commentary on eternal topics like the limits of love and the meaning of commitment."^[1]

The play was commissioned and originally staged by South Coast Repertory, Costa Mesa, California in January 1988. After revisions to the script and direction, the official version opened off-Broadway at Circle Repertory Company on March 14, 1990 (February 20 previews) starring Alec Baldwin, Mary-Louise Parker, Debra Monk, L. Peter Callender, Craig Bockhorn, Michael Warren Powell and John Dossett, and directed by Norman René, who had directed at South Coast Repertory.^[3]

After receiving rave reviews,^[2] the production moved to the Helen Hayes Theatre on Broadway, on May 1, 1990, with Timothy Hutton replacing Baldwin. Other cast members included Barnard Hughes, Debra Monk, John Dossett, and Larry Bryggman. The play closed on May 19, 1991, after 440 performances, received a Tony Award nomination as Best Play, and was a finalist for the Pulitzer Prize for Drama.

A revival was produced in 2003 at the Pacific Resident Theatre in Venice, California.

A revival opened on Broadway at the American Airlines Theatre on March 8, 2007, produced by the Roundabout Theatre Company. Alan Tudyk, Annie Parisse and John Mahoney starred in the lead roles. The show was directed by Daniel Sullivan with original music by John Gromada, scenery by Santo Loquasto, costumes by Jane Greenwood, and lighting by Donald Holder.^[4]

A film version came out in 1992 starring Alec Baldwin and Meg Ryan.

A musical stage adaptation of the story, with a book by Craig Lucas and music by Daniel Messé with lyrics by Messé and Sean Hartley debuted at South Coast Repertory in 2024. The show had been in development since 2016.^[5]

• ​Prelude to a Kiss​ at the Internet Broadway Database