Testosterone (T) and, more potently, dihydrotestosterone (DHT), are in vitro inhibitors of hepatic alcohol dehydrogenase (ADH). An increase in the rate of ethanol disappearance (RED) in man has been observed after orchidectomy. We thus investigated the influence of DHT administration on RED in 10 healthy male volunteers. RED was estimated after an oral ethanol bolus (0.6 g/kg), before and after a 14-day treatment with DHT (2 x 125 mg per day percutaneously; Andractim, Besins iscovesco, France). A mean 11.5-fold increase in DHT levels and a 2.0-fold decrease in T values were observed after DHT administration, confirming the good compliance with treatment. RED was decreased after DHT (0.168 +/- 0.043 vs. 0.137 +/- 0.043 g/l/hr; mean +/- SD; p less than 0.01 using Wilcoxon's paired comparison test). These data are consistent with a DHT-induced inhibition of hepatic ADH in vivo. This could have a beneficial effect by decreasing acetaldehyde production in alcoholic patients, in whom marked hypoandrogenism frequently occurs.