The presence of at least two types of alcohol dehydrogenase has been demonstrated in surgical specimens from the human stomach. One isoenzyme has a Km of approximately 1-2 mM for ethanol comparable to that of class I alcohol dehydrogenase isoenzyme as defined for the liver. This isoenzyme can also be detected by immunohistology using a polyclonal rabbit antibody against human liver class I alcohol dehydrogenase. The other isoenzyme of alcohol dehydrogenase has a much lower affinity to ethanol (greater than 300 mM), but with activities that become significant at ethanol concentrations of more than 100 mM commonly present in the human stomach. Cimetidine was found to be a noncompetitive inhibitor of gastric alcohol dehydrogenase at concentrations as low as 1 mM in vitro. Since the human gastric alcohol dehydrogenase is responsible for the first-pass metabolism of ethanol, its inhibition by cimetidine may explain the reduced first-pass metabolism of alcohol which is associated with elevated ethanol blood concentrations seen after cimetidine therapy.