The response to tricyclic antidepressants (TCAs) is studied in 75 of 121 depressed patients classified as psychotic or nonpsychotic subtypes by Research Diagnostic Criteria. Response was assessed by a clinical global evaluation scale. Of the 75 patients treated with TCAs, 40 (68%) of the nonpsychotic subtype responded in contrast to only 4 (25%) of the psychotic subtype. Adjusting for the effects of chronicity, sex, age, incapacity, agitation, retardation, endogenicity, and the unipolar-bipolar distinction as covariates, it was found that these variables failed to alter the differential response rate of the psychotic and nonpsychotic depressed groups. A literature review of 1054 patients revealed that 67% of the nonpsychotic depressed patients responded to TCAs compared with only 35% of the psychotic depressed patients.