BACKGROUND Nitric oxide (NO) is known to be a signaling molecule with many physiogical functions including apoptotic process regulation. Since apoptosis may contribute to the pathophysiology of schizophrenia, this study was undertaken to determine the plasma concentrations of NO in schizophrenics. METHODS Nitrite/nitrate (NO(2)(-)/NO(3)(-)) concentrations were measured in plasma from 40 patients with schizophrenia, and 36 age- and gender-matched healthy persons using a colorimetric test. RESULTS Plasma NO(2)(-)/NO(3)(-) concentrations were significantly higher in patients with schizophrenia (102.8+/-34.7 micromol/L, p<0.0001) than in controls (69.2+/-13.2 micromol/L). Also, mean NO(2)(-)/NO(3)(-) values in female patients and controls were significantly higher (118.2+/-44.7 micromol/L, p<0.001; 74.8+/-16.1 micromol/L, p<0.05, respectively) compared to males (94.7+/-25.3 micromol/L, 67.6+/-10.8 micromol/L). Significant correlation was seen between plasma NO(2)(-)/NO(3)(-) concentrations and heredity, number of episodes and peripheral blood mononuclear cell (PBMC) caspase-3 activity, which was significantly higher in patients than in controls (p<0.05). There was no significant difference in NO(2)(-)/NO(3)(-) concentrations between patients with different Positive and Negative Syndrome Scale (PANSS) scores or between patients treated with haloperidol (97.2+/-31.2 micromol/L) and those treated with other atypical antipsychotic drugs (109.8+/-33.7 micromol/L). Both parameters showed no significant differences between smokers and non-smokers. CONCLUSIONS This study showed that plasma NO(2)(-)/NO(3)(-) concentrations were significantly increased in patients with schizophrenia, being significantly higher in female than male patients, and showing a significant correlation with heredity, number of episodes and PBMC caspase-3 activity. These results suggest that NO could be considered an inducer or regulator of apoptosis in patients with schizophrenia.