To investigate the effect of age and gender on ethanol metabolism, first-pass metabolism (FPM) and gastric alcohol-dehydrogenase (ADH) activity were compared in 32 elderly and 30 young adult nonalcoholic subjects. The FPM was obtained from the difference between the area under the curve of ethanol blood concentration after intravenous or oral administration of ethanol 0.3 g/Kg b.w. The ADH activity was determined in samples of gastric mucosa obtained during diagnostic endoscopy. In the young adult group the FPM was higher in men than in women (3.3 +/- 2.3 vs 1.2 +/- 0.9 mmol/l/h, respectively, p < .01). In aged subjects FPM was found to be very low for men (1.1 +/- 0.8 mmol/l/h, p < .001); conversely, FPM was not significantly reduced in women (1.7 +/- 0.8 mmol/l/h, p = n.s.). The gastric ADH activity was significantly (p < .01) higher in young adult men than women, whereas in aged subjects the activities were low (p < .0001) in both sexes. Thus, gender-related FPM differences equalize in the elderly or are even reversed, most likely because of gastric mucosal atrophy, which occurs more in men than women.