The long-term effects of d-methamphetamine (MP, 5 mg/kg) on brain mitochondrial monoamine oxidase (MAO) activity were studied in mice given MP intraperitoneally daily for 4 weeks. The MAO activities decreased when serotonin (5-HT) and dopamine (DA) were used as substrates. A marked elevation in MAO activity was seen during MP withdrawal when 5-HT, DA, beta-phenylethylamine (beta-PEA) and norepinephrine (NE) were used as substrates. The kinetics of MAO showed a significant decrease in Km values, but no significant change in Vmax values during MP withdrawal, despite the presence of NE. The Km and Vmax values increased when NE was the substrate. Inhibition of MAO by MP or its metabolites (amphetamine, p-hydroxyamphetamine and p-hydroxymethamphetamine) increased with the use of the following substrates in the order: DA, 5-HT, NE and beta-PEA.