At a dose of 100 mg/kg of cimetidine, the area under the plasma concentration per unit dose (AUC/D) was somewhat larger than those of other doses (12.5, 25, and 50 mg/kg) following bolus intravenous injection in rats. To clarify this phenomenon, the maximum velocity of secretion (V_max) and the Michaelis constant (K_m) for renal excretion were estimated by use of the standard renal clearance method. On the basis of these parameters, the disposition of cimetidine was analyzed by the non-linear 2-compartment model including the tubular secretion process. The observed values of the plasma concentration profile and urinary excretion rate agreed well with the calculated values. V_max (588.2μg/min/kg) and K_m (39.21μg/ml) obtained by the standard renal clearance method were not greatly different from V_max (397.8μg/min/kg) and K_m (62.12μg/ml) obtained by the nonlinear compartment analysis, and the reliability of the model was confirmed. The simulated plasma concentrations based on the linear 2-compartment model agreed well with the values which were simulated based on the non-linear model at doses of 12.5, 25, and 50 mg/kg. Consequently, it is obvious that the disposition of cimetidine following intravenous injection can be approximated as a linear process under the doses of 50 mg/kg. However, at the dose of 100 mg/kg the simulated values based on the linear model were underestimated for the values obtained from non-linear model, and in these cases the approximation of disposition of cimetidine as a linear process will produce an error.