Ketamine is usually administered as a racemate, which is composed of the two isomers, S(+)-and R(-)-ketamine. Recently, we have shown that racemic ketamine at clinical relevant concentrations specifically inhibits the transporter proteins for norepinephrine, dopamine and serotonin heterologously expressed in HEK-293 cells (Nishimura, M., Sato, K., Okada, T., Yoshiya, I., Schloss, P., Shimada, S. and Tohyama, M., Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells. Anesthesiology, 88 (1998) 768-774). Since ketamine interacts stereoselectively with most of its targets, we now investigated whether ketamine also exhibits stereoselectivity on the monoamine transporters. Only the dopamine transporter was found to be stereoselectively inhibited with S(+)-ketamine being almost eight times more potent than R(-)-ketamine (Ki = 46.9 microM for S(+)-ketamine, 390 microM for R(-)-ketamine). In contrast, ketamine exhibited no stereoselectivity for norepinephrine and serotonin transporters.