BACKGROUND Gastric mucosal alcohol dehydrogenase (ADH) may decrease the bioavailability of ingested ethanol. Because this enzyme is found in highest concentrations in the superficial gastric mucosa, diffuse abnormalities of this tissue could lead to a decrease in the first pass metabolism of ethanol. METHODS Thirty-three adult subjects undergoing routine upper gastrointestinal endoscopy had gastric biopsies performed for assessment of gastric histology and the measurement of gastric ADH activity. Twenty of these subjects underwent separate oral dosing and intravenous infusion of ethanol (0.15 g/kg body weight) in order to determine the first pass metabolism, and hence bioavailability, of ethanol. RESULTS Gastric histology was normal in 10 of the biopsies, showed chronic gastritis alone in 13 and significant glandular atrophy (i.e. atrophic gastritis) in a further 10. Gastric ADH activity in specimens with normal gastric histology was significantly higher than those with chronic gastritis (P = 0.02), and was further decreased in those specimens with significant atrophy (P < 0.00001). However, no correlation was found between gastric ADH activity and the first pass metabolism of ethanol (r = 0.09, P = 0.9). CONCLUSIONS These results suggest that although gastric ADH activity was decreased in individuals with abnormal gastric mucosa, ethanol bioavailability was not affected by gastric ADH activity. These data support the view that gastric ADH does not play a significant role in the first pass metabolism of alcohol.