Contractile responses of isolated rabbit aortic strips to epinephrine and norepinephrine were potentiated in a dose-related manner by (+) ketamine but not by (−) ketamine (1.1 × 10−1M - 3.7 × 10−4M). Potentiation was blocked completely by pretreatment with the extraneuronal uptake inhibitor cortisol (83–138 μM) but was unaffected by the neuronal uptake inhibitor cocaine (29 μM). Responses of the rat anococcygeus muscle to these catecholamines were potentiated by both isomers, with (+) ketamine being more potent than its optical antipode. These effects were blocked completely in tissues from 6-hydroxydopamine sympathectomized animals. Results suggest that inhibition of extraneuronal uptake of catecholamines by racecmic ketamine is due solely to an action of the (+) isomer, whereas both isomers appear capable of inhibiting neuronal uptake.