OBJECTIVE Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. The authors measured plasma homocysteine levels in patients with chronic schizophrenia in their catchment area. METHODS A one-way analysis of covariance with age and sex as covariates was performed on the total plasma homocysteine levels of 193 patients with schizophrenia compared with 762 subjects without the diagnosis of schizophrenia who were evaluated in a screening program for employee health. RESULTS The effect of schizophrenia was marked: the mean homocysteine level was 16.3 micro M (SD=11.8) in patients with schizophrenia compared with 10.6 micro M (SD=3.6) in healthy comparison subjects. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients with schizophrenia. CONCLUSIONS Elevated levels of homocysteine in young male patients with schizophrenia could be related to the pathophysiology of aspects of this illness.