1. A stereospecific h.p.l.c. assay of nicoumalone in plasma has been developed. 2. The assay was applied to a study in which 20 mg racemic nicoumalone was given orally to three volunteers and blood samples taken for 168 h. 3. The mean pharmacokinetic parameters of the individual enantiomers were: clearance/bioavailability 1.28 1 h-1, R-enantiomer; 17.5 1 h-1, S-enantiomer: volume of distribution/bioavailability 12.5 1, R-enantiomer; 22.6 1, S-enantiomer: terminal half-life 6.8 h, R-enantiomer; 0.91 h, S-enantiomer. 4. The data are consistent with a substantial first-pass hepatic loss of S-nicoumalone.