This retrospective study evaluates the efficacy of megestrol acetate in patients with hormone refractory metastatic adenocarcinoma of the prostate. Data are presented from 14 patients with advanced prostatic adenocarcinoma who were treated with 160-320 mg of megestrol acetate daily. Each patient was either asymptomatic or had minimal cancer-related symptoms. Disease response was monitored by prostate-specific antigen levels. The response rate was 14%, with two patients having a partial response. No complete responses were observed. The median time to disease progression was 2 months. Our findings when considered together with results from previously published data demonstrate little activity of megestrol acetate in patients with hormone refractory prostate cancer. Therefore, we cannot recommend megestrol acetate as an effective second-line therapy.