We examined whether the distribution of propranolol (PL) exhibits stereoselectivity. (+)-, (-)- or (+/-)-PL was administered by i.v. bolus injection (5 or 10 mg/kg) to rats. The concentrations of PL enantiomers in plasma (Cp) and tissues (e.g., lung, heart, brain, kidney, muscle and gastrointestinal tract) were determined at 5, 10, 30, 60 and 120 min after administration by chiral stationary-phase liquid chromatography. Plasma protein binding of PL enantiomers was evaluated by ultrafiltration. Values of tissue-to-plasma partition coefficient and tissue-to-plasma-free fraction were obtained. Cp for (+)-PL was consistently higher than that of (-)-PL in plasma. In contrast, (-)-PL showed a significantly higher distribution than (+)-PL in all tissues observed (P less than .05) at 60 min after administration of the racemate. As a result, the tissue-to-plasma partition coefficient-Cp curve was markedly different for the two enantiomers. However, because the plasma-free fraction of (+)-PL was less than that of (-)-PL, no remarkable difference was found between the concentration-dependent tissue-to-plasma-free concentration curves for the two enantiomers. In conclusion, our findings suggest that the uptake or binding of PL enantiomers to tissues is saturable and not stereoselective. Therefore, the apparent stereoselective tissue distribution of PL seems to be caused mainly by the difference in plasma protein binding of its enantiomers.