Clinically significant responses after withdrawal of flutamide in patients with hormone-refractory prostate cancer (HRPC) are well documented. Failure to recognize this syndrome of response results in potential morbidity due to salvage therapy, confusion in interpretation of disease state, and introduction of a possible source of error in clinical trials, In this case report, we describe a patient with HRPC whose prostate-specific antigen levels decreased substantially in response to withdrawal of megestrol acetate. Such a response should be considered when megestrol acetate is used in the treatment of HRPC.