The activity of serum angiotensin I-converting enzyme (ACE) was measured in 197 unrelated healthy Caucasian subjects. Plasma ACE activity was correlated with sex, ABO blood groups, and ACE insertion/deletion (I/D) polymorphism. Marked differences in plasma ACE activity levels were observed both among the blood groups and among ACE phenotypes. The corresponding ACE activities were as follows: blood group A, 19.45+/-0.96 (mean+/-SE); O, 20.74+/-1.58; B, 26.17+/-1.40; AB, 24.77+/-1.93 (U/mL: F=4.173; p=0.006983). With ACE genotypes: II, 16.96+/-1.33; ID, 24.25+/-1.05; DD, 27.14+/-1.20 (U/mL; F=6.359; p=0.002165). No difference was observed between men and women. The I/D polymorphism and the ABO system turned out to be two independent (additive) factors influencing plasma ACE activity. Together, they are responsible for 9.56% of the phenotypic variability of ACE. We discuss the role of the ABO system in the known effects of glycosylation of proteins.