Twenty-two patients who had progressive metastatic prostatic carcinoma (Stage D2) despite androgen-deprivation therapy (bilateral orchiectomy, 10 cases; bilateral orchiectomy followed by diethylstilbestrol, 7 cases; diethylstilbestrol, 3 cases; combined megestrol acetate and low-dose estrogen, 2 cases) were treated with ketoconazole. Of 19 evaluable patients, 2 (11%) achieved a partial response (for 6 and 8 months) and 7 others (37%) achieved stabilization of disease (for periods of 3-8 months). Of 16 patients in whom pain was a prominent clinical feature, 13 (81%) noted improvement in pain for periods of one to eight months (median 3 months). We conclude that ketoconazole is a useful addition to our current armory for management of patients with metastatic prostatic cancer resistant to prior hormonal therapy.