4-Methoxytranylcypromine (MeOTCP), a ring-substituted analogue of the monoamine oxidase (MAO)-inhibiting antidepressant tranylcypromine (TCP), was investigated in the rat after chronic (28-day) administration and the results compared with those observed with TCP using equimolar doses of both drugs. At the dose tested, MeOTCP produced a greater inhibition of type A MAO in brain, liver, and heart than did TCP. Both drugs caused a reduction in the specific binding to beta-adrenergic and tryptamine receptors in cortex from brain. MeOTCP produced a marked increase in 5-hydroxytryptamine levels in pons-medulla, hypothalamus, and hippocampus relative to values in vehicle-treated rats and also produced a significant increase in these levels over those observed in the TCP-treated rats.