To investigate the mechanism of the increase in alcohol bioavailability by ranitidine, we determined by nuclear scan the changes in gastric emptying of a 10% ethanol solution (containing 0.3 g ethanol/kg body weight and 300 microCi of technetium-labeled diethylene triamine pentacetic acid) in 8 normal men, before and after treatment with 300 mg ranitidine orally each evening for 1 week. We compared these changes with those of ethanol bioavailability, calculated by integration of the Michaelis-Menten function over the entire alcohol curves after random i.v. and, on a separate day, oral administration of the same ethanol dose, pre- and post-ranitidine. With ranitidine, we found an acceleration of gastric emptying in 7 of 8 subjects, with 20% shortening of the time to 50% emptying (51.8 +/- 4.1 min vs 64.3 +/- 3.4, without ranitidine; P < .001 by paired t test). Despite the disappearance (from the stomach) of most of the dose by the end of the blood alcohol curves, only 83 +/- 4% reached the systemic blood vs 64 +/- 4% without ranitidine (P < .02), most likely because of a shortened exposure of alcohol dehydrogenase to optimal ethanol concentrations. As a result, after oral but not intravenous alcohol administration, ranitidine increased blood alcohol concentrations (29 +/- 4 mg/dl vs 22 +/- 3, without ranitidine; P < .02), with a corresponding decrease in first pass metabolism of ethanol from 107 +/- 16 mg/kg to 47 +/- 16 (P < .01).