The pharmacokinetics of alcohol drinking was studied in male rabbits. Various doses (D) of ethanol (0.25, 0.5, 1, 2 and 3 g/kg BW) were administered perorally to the animals and blood alcohol (ethanol) concentration (BAC) was measured. Simultaneous multiline fitting was attempted using the BAC-time curves of 5 peroral doses and of 5 intravenous doses. The two-compartment open model with parallel first-order and Michaelis-Menten elimination and first-order absorption kinetics was concluded to be the best model. To estimate the value of the absorption rate constant (ka) and the bioavailability (F) at each dose, curve fitting was also attempted by using a single BAC-time curve. The F value decreased with a low dose (0.25 g/kg), but complete systemic bioavailability was noted in higher doses. A first-pass effect was suggested to occur with the low dose. With low doses, the peak BAC might be too low to saturate the ethanol metabolism. The conventional method using area under the BAC-time curve (AUC) underestimated the F value. The other conventional method using theoretical BAC at time zero (C0) [F = C0oral x D(i.v.)/C0i.v. x Doral)] was compared to the AUC method. The estimated F value by this C0 equation method was closer to it by curve fitting than that by the AUC method. The effects of various ka, F and D values were also studied using a computer simulation. Consequently, the conventional AUC method was concluded to overestimate the first-pass metabolism of ethanol. The C0 equation method is thought to be more useful.