OBJECTIVES Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.