The rate of metabolism as well as the metabolic profiles of the enantiomers and the racemate of 2-(2,6-dioxopiperidine-3-yl)-phthalimidine (EM 12), a teratogenic thalidomide analogue, have been investigated in vitro and in the marmoset monkey in vivo. The half-life of racemic EM 12 and of the two enantiomers in vitro (phosphate buffer pH 7.4, 37 degrees C) were all in the same range (12 h). Two major hydrolysis products were found which were formed via amide cleavage of the piperidinedione ring of the molecule (EM 27 and EM 356). Their concentrations were similar. In contrast, EM 356 was the main metabolite of EM 12 present in the urine of marmoset monkeys following single i.p. or p.o. doses of 5 mg/kg b.w. About twice as much EM 356 was produced after administration of R-EM 12 than after administration of S-EM 12. The concentration ratio of the metabolites obtained after p.o. and i.p. administration of the substances were in the same range. Separation of the EM 12 enantiomers present in urine suggests that considerable racemisation took place in vivo, although at a slower rate than in vitro: about 25% of the respective optical antipodes were present 5 h after administration of the R-enantiomer and 7.5 h after administration of the S-enantiomer (compared to 1.5 h in vitro). Our results indicate that racemic EM 12 as well as its enantiomers are chemically and metabolically more stable than thalidomide; however, extensive racemisation occurs both in vivo and in vitro. The metabolism and renal excretion of the enantiomers of EM 12 in the marmoset monkey were shown to be stereoselective.