The long-term effects of endocrine therapy, including polyestradiol phosphate (Estradurin) administration, castration, and their combination, on the circulating concentrations of pregnenolone, dehydroepiandrosterone, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, and androsterone were investigated for 1 year in 22 patients with advanced prostatic carcinoma. Only Estradurin significantly reduced serum concentrations of testosterone, 5 alpha-dihydrotestosterone, and 17 alpha-hydroxyprogesterone. Orchidectomy resulted in a more pronounced decrease in the serum concentrations of testosterone and 5 alpha-dihydrotestosterone; Estradurin combined with orchidectomy led to no additional decrease. There were no consistent changes in the serum concentrations of other steroids measured. It is likely that Estradurin has a direct inhibitory effect on steroidogenesis in Leydig cells, but a significant residual testicular production of testosterone occurred during the period of Estradurin treatment, when given alone. No increase in serum concentrations of adrenal androgens or their precursors was observed during any of the three treatment regimens.