The pharmacokinetics of the enantiomers of mefloquine were studied in the rat after administration of a racemic mixture and of the separate enantiomers (+)-mefloquine and (-)-mefloquine. When 50 mg kg-1 racemic mixture was administered orally for 22 days, plasma concentrations of the (+) enantiomer were 2-3 times higher than those of the (-) enantiomer whereas the opposite was true in every part of the brain (cerebellum, cortex, hippocampus, hypothalamus and striatum). Different concentrations of mefloquine were found in the different regions of the brain; the lowest concentrations of (+/-)-mefloquine (27.0 nmol g-1) were in the cerebellum and the highest (110.0 nmol g-1) in the hippocampus. The main metabolite, carboxymefloquine, was detected in plasma but not in the brain. The results indicate the mefloquine crosses the blood-brain barrier stereoselectively.