Ethanol metabolism increases 2 to 3 hr after the administration of ethanol. This phenomenon, called the swift increase in alcohol metabolism, has been compared in four inbred strains of mice (DBA/2J, C3H/HeJ, AKR/J and C57BL/6J). Basal rates of ethanol elimination were determined in individual mice after an i.p. injection of ethanol (2 g/kg). Little variability in this basal rate of ethanol elimination was observed within each strain. Mice were then exposed to ethanol vapor (20--22 mg/l) and rates of ethanol elimination were determined every 2 hr for 8 hr. By 2 to 3 hr, the rates of ethanol elimination initially increased 2- to 3-fold and then declined toward basal rates over the 8-hr interval in all strains studied. In another experiment, the dose of ethanol was varied to produce blood ethanol levels ranging from 50 to 250 mg/100 ml in both basal- and ethanol vapor-treated mice. Ethanol elimination increased greater than 1.5-fold in all four strains studied when basal rates were compared to rates observed after 4 hr of vapor treatment at the same blood ethanol level; however, the dose at which the maximal increase occurred differed among the strains. DBA/2J mice exhibited a maximal increase in the rate of ethanol elimination when ethanol concentrations were in the range of 30 to 50 mg/100 ml; the increase was smaller as the dose was increased. In contrast, AKR/J and C57BL/6J mice required 100 to 150 mg/100 ml of ethanol to activate the swift increase in alcohol metabolism effect. These data indicate clearly that the swift increase in alcohol metabolism effect is a common phenomenon and that dose and time relations differ in various inbred strains of mice.