Interleukin-12 (IL-12) plays a key role in promoting T helper 1 (Th1) responses and subsequent cell-mediated immunity. Given the role of cytokines in the pathogenesis of psychiatric disorders, the dysregulation of IL-12 in these illnesses would be expected. We measured the plasma levels of IL-12 in 102 psychiatric patients (43 schizophrenia, 34 major depression and 25 bipolar disorder) and 85 normal controls. In addition, IL-12 levels of the patients were measured after an 8-week treatment to assess whether the levels were affected by medication. The IL-12 levels of the patient group with major depression were significantly higher than that of the control group, whereas no differences were found among the other groups. IL-12 values of the three patient groups decreased significantly after 8 weeks of treatment. These findings support the hypothesis that activation of the inflammatory response system and in particular of Th-1-like cells, is involved in the pathophysiology of major depression and that repeated administration of antidepressive and antipsychotic drugs may suppress IL-12 plasma concentrations in psychiatric patients.