The physiological disposition following intravenous dosing of the separate enantiomers of indacrinone-14C (I), and of their major metabolite, 4'-hydroxyindacrinone-14C (M), was studied in the rhesus monkey. Pharmacokinetic analysis indicated that the disposition of I and M was stereoselective. In the case of the enantiomers of I, the areas under the curves of plasma concentration vs. time were about sevenfold greater for the (S)(+)- as compared to the (R)(-)-enantiomer. Renal and plasma clearances of (R)(-)-I were five to seven times greater than those of (S)(+)-I. Total urinary recovery of unchanged drug and metabolite accounted for 70% of the administered dose of either enantiomer. The systemic availability of (R)(-)-M from (R)(-)-I was approximately 21% of the dose, whereas that of (S)(+)-M from (S)(+)-I was only 4%. More pronounced differences were noted in the kinetics of metabolite disposition. The AUC values were about 27 times greater for (S)(+)-M than (R)(-)-M, and the renal and plasma clearances were approximately 25-fold higher for (R)(-)-M as compared to (S)(+)-M. The volume of distribution of (S)(+)-M was only 12% of that observed with (R)(+)-M. There was no evidence of glucuronide or sulfate conjugates of any of the enantiomers. These findings are consistent with the pharmacological activity attributed to the different enantiomers.