OBJECTIVE: To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment. PATIENTS AND METHODS: The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival. RESULTS: Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant. CONCLUSIONS: The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival.