Results of the first randomized trial of the National Prostatic Cancer Project (NPCP) revealed an advantage for cytoxan and 5-FU over standard therapy in hormonally resistant stage D prostate carcinoma. A subsequent trial for patients previously irradiated, receiving the less myelosuppressive agents estracyt or streptozotocin also revealed an advantage over standard therapy. Other completed randomized trials have revealed activity for prednimustine and DTIC. Trials underway for newly diagnosed stage D disease or for stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for cytoxan and DES combined. Current randomized trials in advanced disease are comparing methyl CCNU and hydroxyurea wih cytoxan, and estracyt or vincristine alone or in combination. Chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two trials, comparing the effects of cytoxan or estracyt as long-term therapies with no additional treatment.