Maprotiline, a tetracyclic antidepressant with sedative properties, exhibits strong inhibitory effects on norepinephrine uptake across nerve cell membranes but interferes relatively little with serotoninergic mechanisms. The biological half-life of unchanged maprotiline in blood averages 43 hours. Though several studies suggest a more rapid onset of antidepressant effects with maprotiline than with amitriptyline or imipramine, this issue remains unresolved. The adverse effect profile of maprotiline is similar to that of the tricyclic antidepressants, except that rashes are about twice as frequent with maprotiline as with amitriptyline or imipramine. The most frequent adverse reactions are anticholinergic effects and sedation. Data suggest less frequent and severe anticholinergic side effects with maprotiline than with amitriptyline. Maprotiline may be less likely to induce orthostatic hypotension and tachycardia than standard tricyclic antidepressants, but clinically important differences in cardiovascular effects remain to be conclusively demonstrated. Many patients benefit from the convenience of once daily dosing. Maprotiline is comparable in antidepressant efficacy to the tricyclic antidepressants.