Erythrocyte catechol-O-methyltransferase (COMT) activity has been analyzed in 185 individuals. The activities showed a trimodal frequency distribution. This suggests an autosomal codominant inheritance of the human erythrocyte COMT activity. The mean male COMT activity was 18.9 ± 7.0 (S.D.) nmol/ml RBC/h. The mean female activity was 16.1 ± 6.3 nmol/ml RBC/h and the frequency distribution pattern for women was shifted towards lower values.