Combination of antiandrogen treatment with surgical or medical castration should improve the efficacy of endocrine treatment of prostatic cancer by blocking the effects of adrenal androgens. A nonsteroidal antiandrogen, nilutamide, has shown promising results in preliminary open studies. In a short-term (29 days) comparison of nilutamide plus buserelin and buserelin plus placebo, nilutamide (300 mg/day), significantly reduced bone pain, and fewer patients experienced worsening pain than in the control group. The initial buserelin-induced increase in prostatic acid phosphatase was prevented by nilutamide, but there was a similar increase in testosterone and gonadotropin concentrations to that seen in the control group. Thus, nilutamide can prevent the tumor flare-up associated with the start of luteinizing hormone-releasing hormone (LH-RH) treatment, even though the endocrine responses are not affected. In three multicenter, randomized, double-blind placebo-controlled trials of castration and nilutamide involving 248 patients, the combination of nilutamide and castration decreased bone pain, improved performance status, and increased the number of patients with objective regression, compared with patients who were castrated but did not receive nilutamide. Nilutamide was generally well tolerated, though visual disorders, gastrointestinal disorders, and alcohol intolerance were reported in patients receiving nilutamide. The results suggest that nilutamide improves the efficacy of castration in patients with prostatic cancer. Current studies are investigating the effects of this treatment on survival and the risk-benefit ratio.