The difference in disposition of quinidine (Qd) and its diastereomer quinine (Qn) after intravenous administration was examined in rats at doses ranging from 5 to 20 mg/kg. Dose-dependent kinetics in total clearance and in distribution volume of tissue based on a two-compartment model was observed for Qd; there was no evidence of nonlinearity for Qn. However, there was no significant difference between Qd and Qn for blood clearance at doses of 5 and 10 mg/kg, at which the blood clearances were almost equal to hepatic blood flow for both Qd and Qn since the excretion of Qd and Qn into the urine and bile was minimal. This indicates the elimination of these diastereomers to be non-restrictive in the liver. A concentration dependence in unbound volume of tissue distribution and in plasma protein binding was observed for Qd; there was no concentration dependence for Qn. Although affinity of the drug for components on or within the blood cells was not concentration-dependent for either Qd or Qn, a significantly higher binding capacity for Qn than for Qd was observed attributable to blood cell binding. Based on these results, it is suggested that a larger number of binding sites exist for Qn than for Qd in the body. However, the dissociation binding constant for Qd is much lower than for Qn, resulting in a higher binding of Qd and Qn at low concentrations, with a reversal at high concentrations.