The effect of the concentration of ingested ethanol on the resulting blood alcohol concentrations (BAC) was tested in both humans and rats. In humans, when 0.3 g/kg body weight ethanol was ingested postprandially, the mean area under the blood alcohol curve (AUC) and the mean peak BAC were significantly lower with a concentrated (40% w/v) than with a dilute (4%) solution. Similarly, rats in the fed state exhibited decreasing mean AUCs with increasing concentrations (4%, 16%, and 40%) of intragastrically administered ethanol (1.0 g/kg). Pharmacokinetic analysis comparing intragastric and intraperitoneal administration of ethanol to rats indicated that the more concentrated solution resulted in less alcohol reaching the systemic circulation (4%: 0.896 +/- 0.074 g/kg: 16% 0.772 +/- 0.072 g/kg; 40%: 0.453 +/- 0.037 g/kg) and suggested that this affect could be attributed to two factors: increased gastric retention of ethanol (4%: 0.109 +/- 0.024 g/kg; 16%: 0.102 +/- 0.016 g/kg; 40%: 0.214 +/- 0.042 g/kg) and a large increase in first-pass metabolism (4%; 0.004 +/- 0.054 g/kg; 16%: 0.145 +/- 0.048 g/kg; 40%: 0.329 +/- 0.044 g/kg). In contrast to the results in the fed state, in humans fasted overnight the concentration of alcohol consumed (4%, 16%, and 40%) had no significant effect on mean AUCs. In fasted rats, mean AUCs after intragastric intubation of the two lower concentrations of ethanol (4% and 16%) were comparable to those found after intraperitoneal injection, and only the highest ethanol concentration (40%) produced a lower mean AUC.(ABSTRACT TRUNCATED AT 250 WORDS)