Angiotensin-converting enzyme (ACE) exhibits genetic variation related to insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene. The DD genotype results in high ACE activity and is overrepresented in diseases characterized by left ventricular (LV) hypertrophy and dysfunction. We studied whether the ACE gene polymorphism predicts LV mass or function in the absence of heart disease. Polymerase chain reaction of leukocyte DNA was used to determine the I/D genotype, and M-mode and Doppler echocardiography were used to quantify LV mass and function in 86 human subjects, 36-37 yr of age. All were free of clinical heart disease. The LV mass-to-body height ratio averaged 99 +/- 19 (SD) g/m in subjects with the II genotype (n = 25), 99 +/- 30 g/m in those with the ID genotype (n = 35), and 94 +/- 24 g/m in those with the DD genotype (n = 26; P = 0.790). The indexes of LV systolic and diastolic function were also unrelated to the ACE genotype. We conclude that in the absence of heart disease the ACE gene variation has no major influence on LV mass or function that is detectable at echocardiography.