The activities of monoamine oxidase (MAO)-A and MAO-B (using [3H]serotonin and [14C]beta-phenylethylamine, respectively, as substrates) were determined in homogenates of whole mouse brains using a solvent extraction procedure. 6-Methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-TH beta C) had an IC50 of 1.6 microM, in vitro, for MAO-A using whole brain homogenate. A time course of apparent in vivo MAO-A inhibition using 6-MeO-TH beta C (100 mg/kg i.p.) showed a maximal inhibition by 1 h (56%), a decline to 30% at 12 h, and no inhibition at 24 h. There was a maximal inhibition of MAO-B by 4 h (16%). A dose-effect study done at 1 h after injection showed 6-MeO-TH beta C to inhibit MAO-A by 23% at 25 mg/kg, 43% at 50 mg/kg, 58% at 100 mg/kg and 73% at 150 mg/kg; for MAO-B there was no inhibition at 25 and 50 mg/kg and 16% inhibition at 100 mg/kg. The data thus indicate that, at doses less than or equal to 50 mg/kg, 6-MeO-TH beta C is a specific MAO-A inhibitor in vivo.