Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Determination of total antioxidant status (TAS) provides an index of the sum of activities of all antioxidants. However, there have been few systematic studies to examine the relationship between TAS levels and psychopathology in first-episode and drug-naive patients with schizophrenia. TAS levels were determined in the plasma of 60 never-medicated first-episode patients with schizophrenia and 68 healthy control subjects. The schizophrenia symptomatology and the depressive symptoms were assessed by the positive and negative syndrome scale (PANSS) and the Hamilton rating scale for depression (HAMD). The results showed that TAS levels were significantly lower in first-episode patients with schizophrenia than in healthy control subjects (159.8 ± 45.8 U/ml vs 211.4 ± 46.8 U/ml, F=39.5, df=1, 126, p < 0.001). A trend toward significant inverse correlation between TAS levels and PANSS negative subscore was observed (r = 0.25, df=60, p = 0.06). Our results suggest that oxidative stress occurs in an early course of schizophrenia and may have an important role in pathogenesis and perhaps, negative symptomatology of schizophrenia.