It has been postulated that major depression may be accompanied by significant changes in cell-mediated and humoral immunity related to the pathophysiology or pathogenesis of that illness. We explored the role of 2 cytokines, IL-12 and TGF-β1, which represent the cytokines of the Th1 and Th3 types, in the pathophysiology of major depressive disorder (MDD). Cytokine levels were measured in 30 major depressed patients at the time of admission and 6 weeks after effective antidepressant treatment; levels were measured once in 30 normal controls. At the time of admission, TGF-β1 levels of MDD patients showed no differences from normal controls, but IL-12 was significantly higher than in normal controls. However, the IL-12/TGF-β1 (Th1/Th3) ratios of depressed patients were not different from those of controls. In MDD patients, IL-12 values were significantly decreased after treatment, while TGF-β1 levels were significantly increased. IL-12/TGF-β1 ratios of patients were significantly decreased after treatment compared with before treatment. There were no significant correlations between changes in the cytokine levels and changes in scores representing the severity of depression. These findings suggest that major depression is accompanied by immune activation during the acute depressed state, and antidepressant treatments have anti-inflammatory effects.