Abstract The isomers of tranylcypromine (TCP) readily entered the rat brain after intraperitoneal administration and reached peak concentrations within 15 min. Apparently, (−) TCP entered the brain more rapidly and reached somewhat higher concentrations than (+) TCP. Alter a dose of 2.5 mg/kg of (−) or (+) TCP. there was significantly more drug in brain than has been reported necessary to block the re-uptake of amines by synaptosomes. Both isomers blocked monoamine oxidase in vivo and in vitro. (+) TCP was between 10 and 60 times more active than (−) TCP, depending on the amine substrate evaluated, and both isomers were better inhibitors of type-B monoamine oxidase activity than type-A activity. The (+) isomer was more active in preventing reserpine-induced sedation in the rat than the (−) isomer. The ability to prevent the rescrpine syndrome was apparently related to the ability of the drugs to block monoamine oxidase activity rather than to blockade of amine re-uptake.