Patients with depressions accompanied by delusional thinking are reported to respond poorly to tricyclic antidepressants. We present four cases of delusional depression successfully treated with tranylcypromine. Three patients had previously been treated unsuccessfully with adequate trials of tricyclic antidepressants and one had been treated with a tricyclic-phenothiazine combination with a poor response. These four patients experienced a dramatic reduction in depression and delusional thinking when treated with tranylcypromine. On the basis of these cases, tranylcypromine appears to be an effective treatment for some patients with delusional depressions.