Abstract: Disposition kinetics of procainamide (PA) and its metabolite Nacetylprocainamide (NAPA) in rats was simultaneously predicted by a physiological pharmacokinetic model. The parameters, such as clearances in kidney and liver and tissue/blood concentration ratios, which were needed for simulations, were determined. The estimated clearances of PA in rat blood, kidney and liver were 47. 28, 13. 56 and 33.71 ml· kg^-1·min^-1, respectively. Tissue/blood drug concentration ratios were obtained after ⅳ administration according to Gallo's method and demonstrated that heart,liver, kidney, muscle and small intestine have greater affinity for PA than do blood components.The concentrations of PA and NAPA in rat tissues following iv administration of PA ·HCl 75 mg/kg were predicted and compared with observed values. The results showed that a good agreement between predictions and observed data was found in most of rat tissues. Concentrations of PA and NAPA in plasma of man, based on scaling-up of kinetics of PA and NAPA from rat to man, was also simulated.