Psychotic depression is a distinct clinical entity in that its response to tricyclic antidepressants is poor but its response to tricyclic antidepressant-antipsychotics is better. The authors report the favorable outcome of four patients with psychotic depression treated with amoxapine, a derivative of the antipsychotic loxapine. The elevation of serum prolactin during treatment in three patients suggests that postsynaptic dopamine blockade occurs with amoxapine treatment. This might account for the efficacy of amoxapine in psychotic depression.