Healthy men have a larger endogenous cortisol production rate (PR) than healthy women. To investigate whether this sex-specific difference is maintained in men with low serum testosterone concentrations the endogenous PRs (2 pm to 6 pm) of testosterone, dihydrotestosterone (DHT), and cortisol were simultaneously determined in 10 hypogonadal men. As expected, hypogonadal men were characterized by subnormal PRs of testosterone (19.6 +/- 5.7 microg/h; normal, 180 to 346 microg/h) and of DHT (1.6 +/- 1.1 microg/h; normal, 11 to 20 microg/h). In hypogonadal patients with an intact pituitary-adrenal axis (n = 8), plasma concentrations (7.3 +/- 1.8 microg/dL), metabolic clearance rates (MCRs) (10.0 +/- 4.6 L/h), and endogenous PRs (0.6 +/- 0.2 mg/h) of cortisol were comparable to those seen in eugonadal men. Hence, the sex-specific difference in endogenous cortisol PRs does not depend on the prevailing serum concentrations and on the endogenous PRs of testosterone.