Accumulating evidence suggests BDNF as a molecule involved in the pathophysiology of schizophrenia. To examine the BDNF levels and the relationship between BDNF levels and psychopathology in patients with schizophrenia, 81 physically healthy patients with schizophrenia were compared with 45 age-, sex- matched normal controls. The psychopathology of patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF-like immunoreactivity were significantly lower in medicated patients with chronic schizophrenia than in healthy control subjects. A significant negative correlation between BDNF-like immunoreactivity and PANSS negative subscore was observed. As compared with normal controls, there was a significant decrease in BDNF-like immunoreactivity in patients treated with both atypical and typical antipsychotics. However, no correlation between standardized drug doses and BDNF-like immunoreactivity was found. These findings suggest that serum BDNF levels in chronic schizophrenia under antipsychotic medication may be decreased. However, long-term effects of antipsychotics remain to be characterized.