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Aims: Thiopentone is administered as a racemate (rac-thiopentone) for induction of anaesthesia as well as for neurological and neurosurgical emergencies. The pharmacokinetics and pharmacodynamics of rac-thiopentone have been extensively studied but the component R-(+)- and S-(-)- enantiomers, until very recently, have been largely ignored., Methods: The present study analyses the pharmacokinetics of R-(+)- and S-(-)-thiopentone in 12 patients given rac-thiopentone intravenously for induction of anaesthesia and five patients given a prolonged infusion of rac-thiopentone used for treatment of intracranial hypertension., Results: The mean total body clearance (CLT) and apparent volume of distribution at steady-state (Vss) showed trends towards higher values for R-(+)- than for S-(-)-thiopentone in both patient groups; CLT and Vss of unbound fractions of R-(+)- and S-(-)-thiopentone, however, did not show these trends. The time courses of R-(+)- and S-(-)- thiopentone serum concentrations were so similar that EEG effect could not be attributed to one or other enantiomer. Serum protein binding for S-(-)-thiopentone was greater than for R-(+)-thiopentone (P = 0.02) and 24 h urinary excretion of R-(+)-thiopentone was greater than for S-(-)-thiopentone (P = 0.03). In one patient, concomitant measurement of CSF and serum thiopentone concentrations found that serum: CSF equilibration of unbound fractions of both enantiomers was essentially complete., Conclusions: The study was unable to determine any pharmacokinetic difference of clinical significance between the R-(+)- and S-(-)-thiopentone enantiomers and concludes that minor differences in CLT and Vss could be explained by enantioselective difference found in serum protein binding.