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OBJECTIVE: Altered glycine and homocysteine levels may contribute to N-methyl-d-aspartate receptor dysfunction in schizophrenia. The authors measured plasma levels of these amino acids in a group of patients with chronic schizophrenia and related them to the patients’ symptom profiles and types of antipsychotic medication. METHOD: Plasma levels of amino acids in 94 patients with schizophrenia were compared with those in 34 age- and sex-matched normal subjects. The Positive and Negative Syndrome Scale was used to evaluate the patients’ psychopathology. RESULTS: Plasma glycine levels and glycine-serine ratios were lower and homocysteine levels were higher in patients than in comparison subjects. Low glycine levels correlated with a greater number of negative symptoms. The glycine-serine ratios of normal subjects and patients being treated with clozapine did not differ significantly. CONCLUSIONS: These findings support the hypothesis that altered levels of glycine and homocysteine may coexist in patients with schizophrenia and contribute to pathophysiological aspects of this illness.