The authors determined the erythrocyte catechol O-methyltransferase (COMT) activity of 38 chronic schizophrenic patients, 69 of their first-degree relatives, and 39 normal controls. COMT activity did not distinguish patients from controls. Within families, COMT activity was not associated with schizophrenia spectrum disorders. The data suggest that COMT activity is not an indicator of vulnerability to schizophrenia.