The results of a large randomized prospective clinical trial conducted by the Veterans Administration Co-operative Urological Research Group (VACURG) in 1968 are updated and reevaluated. In this study, placebo, diethylstilbestrol (DES, 5 mg/day), orchiectomy plus placebo, and orchiectomy plus DES were compared in patients whose conditions were initially diagnosed as stage III and IV carcinoma of the prostate. Results showed that orchiectomy alone or in combination with estrogen did not improve overall survival rates in stage III and IV carcinoma of the prostate. In the two treatment groups receiving estrogen, however, there were fewer deaths due to cancer of the prostate, but this effect tended to be offset by an increased number of deaths due to cardiovascular causes. Deaths from other causes showed no particular pattern with respect to treatment. These studies showed that estrogen is more effective than orchiectomy in preventing deaths from cancer and that the addition of orchiectomy to estrogen does not offer any clear-cut advantage over estrogen therapy alone. If cancer symptoms necessitate treatment, initial therapy with estrogen is preferred. Orchiectomy should be reserved for those circumstances in which a patient is not reliable, cannot tolerate estrogens, or has severe cardiovascular disease.