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Accumulating evidence indicates that altered one-carbon metabolism occurs in schizophrenia. Plasma total homocysteine (Hcy) is attracting increased attention. Elevated plasma Hcy levels have been proposed as a potential hey substance in schizophrenia.This study was carried out to confirm the results of previous research on schizophrenia that reported high serum Hcy levels and to test the impact of increased plasma Hcy levels on the symptom profile in first-episode schizophrenic male patients at index hospitalization. Other aims included investigating baseline Hcy level as a potential marker predicting schizophrenia outcome 1 year following index hospitalization.The study prospectively investigated a group of 50 male patients with first-episode schizophrenia. These patients were compared with 50 apparently healthy male participants, matched for age, sex, and ethnicity, who served as controls. The diagnosis was made according to the ICD-10 Diagnostic Criteria for Research through conducting Mini International Neuropsychiatric Interview. Anthropometric indices and biochemical parameters including plasma Hcy levels were determined using a standard procedure. The patient group was divided into a patient group with high serum Hcy levels and a patient group with normal serum Hcy levels. Both patient groups were compared at baseline and at 1 year for demographic, clinical, and treatment characteristics.Male patients diagnosed with first-episode schizophrenia have significantly higher plasma Hcy levels more sel than healthy controls. The percentages of schizophrenic patients with high Hcy levels were 40%, whereas 60% showed normal plasma Hcy levels. The patient group with increased plasma Hcy levels presented with significantly increased severity of psychopathology and treatment characteristics at index hospitalization compared with those with normal serum Hcy levels. Multiple regression analysis showed that altered plasma Hcy levels are associated with more severe psychopathology and less favorable outcome in a 1-year follow-up study.We found higher rates of Hcy in patients with first-episode schizophrenia compared with matched controls. Our results suggest that Hcy might play a role in the pathogenesis of schizophrenia and may negatively influence outcome in terms of symptom severity and treatment characteristics; future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of Hcy levels in first-episode schizophrenia and for the development of appropriate management strategies.