The influence of a 7-day medication of either cimetidine (1,000 mg per day) or ranitidine (300 mg per day) on serum ethanol concentrations after a single oral dose of ethanol (0.8 gm per kg body weight) was investigated in a randomized placebo-controlled study in eight male volunteers. Compared with the placebo, cimetidine but not ranitidine produced a significant increase in both the peak serum ethanol concentration (85.9 +/- 3.5 vs. 73.0 +/- 3.2 mg dl-1, p less than 0.02) and in the area under the serum ethanol concentration time curve (350 +/- 19 vs. 304 +/- 25 mg dl-1 hr-1, p less than 0.05). However, the ethanol elimination rate was not affected by cimetidine. When ethanol (1.0 gm per kg body weight) was administered intravenously, cimetidine failed to induce a change in ethanol metabolism. Furthermore, the effect of H2-receptor antagonists was studied in animal experiments. Female Sprague-Dawley rats received a single dose of ethanol (7 or 3 gm per kg body weight) together with an intraperitoneal injection of either cimetidine (120 mg per kg body weight), ranitidine (120 mg per kg body weight) or isotonic saline. After alcohol absorption, ethanol elimination was significantly inhibited by both cimetidine (3.99 +/- 0.39 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) and ranitidine (4.21 +/- 0.14 vs. 5.68 +/- 0.23 mmoles kg-1 hr-1, p less than 0.02) at high ethanol concentrations (60 to 20 mM) but not at blood ethanol concentrations below 20 mM.(ABSTRACT TRUNCATED AT 250 WORDS)