Bupivacaine, being a racemic local anesthetic, exists as an equal mixture of its component enantiomers R(+)- and S(-)-bupivacaine, which behave pharmacokinetically as independent drugs after injection into the body. Intercostal neural blockade using bupivacaine was performed for postoperative analgesia in 12 patients after orthotopic liver transplantation. Arterial blood, sampled serially, was assayed by enantioselective high-performance liquid chromatography for R(+)- and S(-)-bupivacaine. The average of the simultaneous R(+):S(-) ratios of blood bupivacaine concentrations in the 12 patients was 0.74 (SD 0.11); however, the use of a population mean value or a mean value for any patient denies the time-dependence of this entity. The blood enantiomer concentration difference was reflected in the maximum measured concentrations which, after the first dose, were, respectively, 0.38 (SD 0.19) and 0.52 (SD 0.28) mg.L-1.100 mg-1 RS-bupivacaine administered (P = 0.0003). The difference in blood concentrations between the enantiomers, reflected by the R(+):S(-) ratio being less than unity, could be explained by a greater mean total body clearance and a larger apparent volume distribution of R(+)-bupivacaine. Elimination of both enantiomers was prolonged in these patients after liver transplantation compared to data from the literature, but there was no tendency for either enantiomer to accumulate selectively, even upon repeated dosing. We conclude that this demonstration of differences in pharmacokinetics (and, in laboratory studies, also in pharmacodynamics) between the bupivacaine enantiomers points to the need for future studies to recognize the enantiomeric duality of this local anesthetic.