We recently observed a familial influence on the plasma concentration of sex-steroids and the metabolic clearance in men with prostatic cancer. We have now determined, by isotope dilution techniques, the blood estradiol and testosterone production and clearance rates in men with prostatic cancer and in unrelated controls. Thirty-eight men had a diagnosis of prostatic cancer before the age of 63, and 22 controls matched for age were randomly selected from the general population. None of the patients or controls had received endocrine therapy. The plasma content of testosterone, dihydrotestosterone, estrone, estradiol, 3 alpha-androstanediol glucuronide, dehydroepiandrosterone sulfate, sex-hormone binding globulin, apparent free testosterone concentration, follicle stimulating hormone and luteinizing hormone were not significantly different between the groups. The metabolic clearance and production rates of testosterone were significantly (P = 0.008 and P = 0.013, respectively) higher in patients [447 +/- 26 L/day/body surface area(m2) and 2.21 +/- 0.17 mg/day/m2, n = 38] than in controls [346 +/- 20 L/day/m2 and 1.70 +/- 0.11 mg/day/m2, n = 22]. The PR and MCR of estradiol were not significantly different between patients with prostatic cancer (n = 19) and controls (n = 12). These results indicate that men with prostatic cancer have elevated clearance and production rates of testosterone without an alteration of estradiol production or clearance.