SummarySignificant sibling-sibling and within-family correlations of human red blood cell catechol-o-methyl transferase activity have suggested a high degree of genetic control over levels of activity of this catecholamine-related enzyme. However, family studies do not disentangle genetic from environmental similarities as causative of within-family correlations. We therefore undertook a human twin study using the monozygotic-dizygotic comparison method. Twelve pairs of monozygotic twins had an intraclass correlation of .90 in red blood cell catechol-o-methyl transferase activity, and seven pairs of dizygotic twins had an intraclass correlation of .37. Heritability of the enzyme activity was estimated by different methods as between 68–100 per cent.