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. 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. 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. 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.