Recently, there were some reports that major depression is accompanied by signi®cant alterations in the percentage and number of peripheral blood mononuclear cells (PBMCs), such as increased number of CD4 T cells, B cells (e.g. CD19 , CD21 ), number of leukocytes, monocytes and neutrophils and an increased CD4 /CD8 T-cell ratio. The aims of the present study were to examine the number and percentage of PBMCs in major and treatmentresistant depressed (TRD) patients and the eects of antidepressant treatments on those PBMCs. Major depression was characterized by a signi®cantly higher number of leukocytes and CD4 T-cells, a higher percentage of CD2 T cells and CD4 T cells, and a higher CD4 /CD8 T-cell ratio than normal controls. Patients with TRD had a signi®cantly higher percentage of CD4 T cells and CD4 /CD8 T-cell ratio, and a signi®cantly lower percentage of CD8 T cells than non-TRD patients and normal controls. There were signi®cant negative correlations between the length of the index episode or duration of illness and number or percentage of monocytes. Subchronic treatment with antidepressants signi®cantly reduced the number of leukocytes and neutrophils, but had no eect either on the absolute number of the other PBMCs or on the CD4 /CD8 T-cell ratio. The results suggest that (i) the higher CD4 /CD8 T-cell ratio in major depression is a trait marker of that illness and of treatment resistance; (ii) the increased numbers of leukocytes and neutrophils are state markers of depression and are reduced by `subchronic' antidepressant therapy; (iii) the number and percentage of monocytes decrease with respect to duration of illness and length of the index depressive episode. # 1997 by