Cross-sectional population studies reported decreased mitogen-induced lymphocyte responsiveness in severely depressed patients. This immunologic impairment, indicative of T- and/or B-cell dysfunction, was related to disturbances in the dexamethasone suppression test (DST) and to age effects. Glucocorticoid overdrive, a hallmark for severe depression, exerts immunosuppressive effects through the impact on neutrophils, lymphocytes, and monocytes and natural killer cells (NKC). This paper has analyzed the relation of peripheral blood immune parameters to severe depression, DST results and age. The population consisted of 37 inpatients categorized according to DSM-III as minor depression (300.40, 309.00), simple major depression (296.X2) or major depression with melancholia and/or with psychotic features (296.X3, 296.X4). The number of leukocytes, neutrophils, lymphocytes and monocytes was counted. T-cell (total T-cell, T-helper, T-suppressor, HLA-DR), B-cell (LN1 and immunoglobulin (Ig) receptors), monocytes (M1 and M3 membrane antigens) and NKC activity were identified by phenotype using monoclonal antibodies. No differences were detected between the depressive subgroups for any of the parameters examined. There were no relationships between these immune variables and the severity of illness, DST results or age.