Dihydrotestosterone (DHT) levels were measured by RIA in tumor tissue from 32 men with advanced prostate cancer and correlated with their clinical responses to antiandrogen therapy. In 24 patients with tumor tissue DHT levels greater than 2.5 ng/g, 20 initially responded to therapy with partial objective regression or were objectively stable for 12 or more months, while 4 patients relapsed in less than 1 yr. The average disease-free interval in this group was 24 months, with 9 patients still continuing in partial objective regression or objective stability. Of 8 patients with DHT levels less than 2.0 ng/g, 5 had either objective progression or were objectively stable for 6 months or less; 2 other patients have completed remissions ranging from 16-24 months, while 1 patient remains objectively stable for 21 months to date. The average disease-free interval in patients with DHT levels less than 2.0 ng/g was 9.75 months, which is significantly less (P less than 0.001) than that of patients with DHT levels greater than 2.5 ng/g. There was no discernible relationship between the Gleason histological grade of prostate cancer and initial clinical response to therapy in these same patients. In summary, this study supports the thesis that tissue DHT levels may be a useful marker for predicting the clinical response of prostate cancer to antiandrogen therapy.