Cellular origins of methylarginines are not precisely known but the presence of free methyl and dimethylarginines in the brain were reported. We have investigated the circulating concentrations of asymmetrical dimethylarginine NG,NG-dimethylarginine (ADMA), NG,NG-dimethylarginine (SDMA), nitrate and nitrite levels in drug naive first episode schizophrenic patients and matched control subjects. Three of those patients were treated with neurolepties for 3 months. Plasma ADMA levels increased significantly but nitrate levels were significantly low compared to control subjects. Drug treatment apparently lowered ADMA levels and increased nitrate levels in plasma. Methylation of arginine to methylarginines may have an important role in regulating signal transduction through the nitric oxide system in the brain, and suggest novel therapeutic targets.