Plasma DBH activity was studied in patients with affective illness (unipolar or bipolar) and in their families. We found diagnosis, mood state or lithium treatment did not modify plasma DBH activity. In family studies we found same-sex siblings to show significant correlations for plasma DBH activity regardless of diagnosis. Monozygotic twins had almost identical DBH activities; 4 pairs of monozygotic twins discordant for affective illness were concordant for DHB activity. The heritability estimate for plasma DBH activity is greater than 0.90, indicating a strong genetic influence. These studies reveal that affective illness does not modify plasma DBH activity and that familial factors play an important role in controlling plasma DBH activity.