Myocardial uptake of thiopental enantiomers by an isolated perfused rat heart preparation was examined after perfusion with protein-free perfusate. Outflow perfusate samples were collected at frequent intervals for 20 min during singlepass perfusion with 10 p,g/ml racemic thiopental (washin phase) and for another 45 min during perfusion with drug-free perfusate (washout phase). (+)-and (-)-thiopental concentrations were assayed by chiral high-performance liquid chromatography. Heart rate, perfusion pressure, and electrocardiogram were also monitored. During the washin phase, there was no significant difference between the mean values of the equilibration rate constants of (+)-and (-)-thiopental enantiomers (0.44 ? 0.07 min-I and 0.43 ? 0.09 min-', respectively, P > 0.05). Mean volumes of distribution of (+Iand (-)-thiopental enantiomers were similar (6.34 2 1.20 and 6.45 2 1.29 ml/g for the washin phase and 7.22 2 0.71 and 7.47 2 0.81 ml/g for the washout phase, respectively, P > 0.05). This indicates that tissue accumulation of thiopental enantiomers in the isolated perfused rat heart was not stereoselective. Uptake of thiopental by the heart was perfusion flow rate-limited and independent of capillary permeability. These findings suggest that myocardial tissue concentration of racemic thiopental should be an accurate predictor of myocardial drug effect. o 1996 Wi~ey-~iss, Inc.