The original transmethylation hypothesis of schizophrenia has evolved with time and experiment to the present concept that a defect in the methyl-carbon metabolic pathway may be causative in this illness. Various researchers have proposed that specific steps in the methyl-carbon pathway may be defective, and have presented evidence to support these possibilities. We have tested the general concept of the hypothesis by administering methionine labeled with 11C or 14C in the S-methyl carbon to patients with schizophrenia and to controls and measured the expiration of 11CO2 and 14CO2. We found that the rate and total expiration of labeled CO2 were three times less in the patients than in the controls, with no overlap of data points in the two groups. Specific steps in the methylcarbon pathway that might be defective and produce the results seen here are discussed in light of this and other researchers' findings.