The Blaylocks, Miriam (Catherine Deneuve) and John (David Bowie), are a well-to-do couple in early 80s New York City. They give cello lessons by day, and by night prowl the discos of Manhattan looking for young and gorgeous people, not for sex, but for blood. Miriam and John are vampires, and Miriam has a great power. She's lived for over 4,000 years, and as she takes lovers, she can give them the gift of a very long life, until she gives up interest in them.

Miriam has grown tired of John, and so he begins aging. He goes to a doctor named Sarah Roberts (Susan Sarandon), who is well-known for studying aging, and as she studies his case, she finds herself drawn into Miriam's world.