The efficacy of total androgen blockade using orchiectomy and nilutamide was compared with orchiectomy with placebo in a large double-blind clinical trial with 457 patients. The median interval to objective progression was 20.8 months for total androgen blockade and 14.7 months for orchiectomy alone (P = 0.0041). The median interval to death for all patients was 37.1 months versus 29.8 months (P = 0.041). Decrease in pain was seen at months 1, 3, and 6 in a significant percentage for the total androgen blockade group. A significant difference in prostate specific antigen levels was seen at months 3 and 6, with normalization of 75% and 28%, respectively, in both groups at both times. The tolerance of the nonsteroidal antiandrogen nilutamide showed visual disturbances as a side-effect, resulting in the withdrawal of five patients from treatment. Liver and lung disturbances were transient. Total androgen blockade is a more effective treatment for metastatic prostate cancer than orchiectomy alone in this study population.