Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.