One hundred and fifteen human male subjects, 19-30 years of age, received ethanol orally as vodka (0.55, 0.7, or 0.85 g/kg) followed by a second drink (0.3-0.4 g/kg) given 3-4 hr later. After both doses, blood ethanol levels reached approximately 100 mg/dl. Breath samples were taken every 20-30 min and rates of ethanol elimination were determined. In addition to the design described above, 100 subjects received 0.7 g/kg ethanol in two separate visits to the laboratory. In a third experimental design, ethanol was given i.v. to 12 subjects. With the single-day experimental design, the frequency distribution of changes in rates of ethanol elimination between the first compared with the second administration of ethanol was not unimodal. Up to 20% of the subjects demonstrated rates more than 40% greater than basal values in response to ethanol. Based on these findings in humans, a Swift Increase in Alcohol Metabolism (SIAM) was defined as an increase in the rate of ethanol elimination of at least 40% over the basal rate. Under these conditions, the frequency of SIAM was dose dependent (studied with 0.55, 0.7, and 0.85 g/kg); nearly 20% of the subjects demonstrated SIAM with a dose of ethanol of 0.85 g/kg. In the two-day experimental design, a SIAM response was also observed in about 10% of 49 well-fed subjects; however, none of 51 subjects tested exhibited a SIAM response following an overnight fast. In addition, a rapid and transient SIAM reflecting a 60% increase in the rate of ethanol elimination above basal values was observed when ethanol was given continuously for 5 hr i.v.(ABSTRACT TRUNCATED AT 250 WORDS)