The disposition and metabolism of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), a new agent with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties, was studied in rats, dogs, and rhesus monkeys. [3H]benzene-MK-801 was administered orally at a dose of 1 mg/kg. MK-801 was measured in plasma by GLC using a nitrogen detector; the overall sensitivity of the method was 3 ng/ml. Radioactivity was excreted mainly in urine of dogs and monkeys but fecal excretion in rats was also extensive. The apparent plasma t1/2 of MK-801 in the rat and dog was approximately 1 hr. Maximal plasma levels of MK-801 in the rat, dog, and monkey were 46 (0.5 hr), 16 (0.25 hr), and 10 (2 hr) ng/ml, respectively. Radioactivity was extensively excreted in rat bile and was widely distributed among various tissues. Major metabolites of the drug in rat and dog urine were the 2- and 8-hydroxy analogs (rat) and the N-hydroxy derivative (dog).