We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with imipramine or desipramine (100-150 mg/day) resulted in a dramatic increase in the plasma concentrations of the tricyclic antidepressants associated with adverse effects. These observations indicate that fluvoxamine inhibits both the demethylation of imipramine and, possibly to a lesser extent, the hydroxylation of desipramine. The combination of fluvoxamine with tricyclic antidepressants should be avoided whenever possible.