This retrospective study describes the response of 13 delusional unipolar depressives to combination antipsychotic-tricyclic antidepressant drug therapy. The Research Diagnostic Criteria were used by two independent raters to verify the presence of a delusional, primary, unipolar, major depressive disorder. Thirteen patients met the criteria and received combined antipsychotic-antidepressant pharmacotherapy. Twelve of the 13 responded. This contrasts sharply with the low response rate described for delusional depressives when treated with tricyclic antidepressants alone. Descriptive characteristics of the delusional depressives were compared with those of a group of nondelusional unipolar depressives. Delusional depressives had histories of a greater number of prior depressive episodes and more of the delusional depressives demonstrated a psychomotor disturbance.