In an open pilot study of 21 therapy-resistant depressive inpatients, plasma levels of antidepressants were determined during treatment with a combination of moclobemide/ trimipramine (n = 15) and moclobemide/maprotiline (n = 6). After combined administration of trimipramine and moclobemide (MCB), a significant increase in the plasma level of trimipramine (39%) was observed. After combination of maprotiline with moclobemide, maprotiline levels were increased (25%, n.s.). The results show that moclobemide, as an inhibitor of isoenzymes of the cytochrome P 450 oxidase, can cause increases in the plasma levels of tricyclic and tetracyclic antidepressants. No correlation between the serum level of the antidepressants and treatment outcome was found in this open study.