A 66-year-old man with androgen-independent prostate cancer was treated with abarelix, a gonadotropin-releasing hormone antagonist, for 20 weeks in an experimental protocol. He did not respond to therapy, but his serum prostate-specific antigen level dropped from 15.8 ng/mL to a confirmed 0.8 ng/mL after abarelix was stopped. His prostate-specific antigen level did not return to greater than 15.8 ng/mL for 14 months. This is the first report of a withdrawal response after therapy with a gonadotropin-releasing hormone antagonist, a new class of agents for prostate cancer. Additional observations are needed to determine whether this is an isolated case or a harbinger of a more common phenomenon.