Patients diagnosed as having benign prostatic hyperplasia (BPH) had determination of prostate volume (PV), prostate-specific antigen (PSA), and serum testosterone before consideration for entry into a double-blind, randomized trial of flutamide (750 mg/day for 6 months). The mean PSA level for these patients (N = 43) was 7.6 ng/ml (range: 1.0 to 45.7), and the mean PV was 76.8 cm3 (range: 24 to 198). Linear regression analysis demonstrated a strong correlation between the two (r = 0.876, P less than 0.05). Every 10 cm3 of prostate volume accounted for 1.02 ng/ml of PSA in the serum. Twenty-two patients (11 treated with flutamide, 11 with a placebo) agreed to enter the study. Prostate volume decreased by 35% and PSA by 65% (P less than 0.001) within 6 months. These changes occurred despite a 58.3% increase in serum testosterone levels (P less than 0.01). Patients treated with a placebo experienced no significant changes. Side effects were minimal, and flutamide was well tolerated. These data suggest that androgen deprivation therapy with flutamide may be an effective and safe treatment for BPH.