1. Recently, the authors have reported that severe depression may be accompanied by a systemic immune activation with an increase in the number of T cells expressing activation receptors. 2. The present large-scale study examines specific T (CD2+HLADR+ and CD7+CD25+) and B (CD7-CD25+) cell activation markers in depressed inpatients and normal volunteers together with the number of leukocytes and monocytes. 3. The authors have established that depression is characterized by a significantly increased expression of T cell activation receptors (CD7+CD25+) and by the appearance of previously unexpressed T cell surface markers (CD2+HLADR+). There was a significant and positive correlation between the number of CD7+CD25+ cells and monocytes, with the expression of the HLADR and CD25 T cell activation markers being significantly and positively correlated. Up to 64% of all depressed subjects exhibit an increased expression of these activation markers with a specificity of 91%. 4. The normal control group and the depressive sample constitute two discrete classes (i.e., qualitatively distinct groups) with respect to the expression of these activation markers and leukocytosis. 5. It is concluded that our results are compatible with the presence of T-cell activation in a considerable number of depressed patients.