We evaluated the correlates of baroreflex sensitivity (BRS) in healthy subjects. The study consisted of 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Baroreflex control of heart rate was measured by using the phenylephrine bolus-injection technique. Frequency- and time-domain analysis of heart rate variability and an exercise test were performed. Plasma norepinephrine, epinephrine, insulin, and arginine vasopressin concentrations and plasma renin activity were measured. In the univariate analysis, BRS correlated with age (r = -0.65, P < 0.001), diastolic blood pressure (r = -0.47, P < 0.001), exercise capacity (r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also a significant correlation between BRS and plasma norepinephrine concentration (r = -0.22, P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to the multivariate analysis, age and gender were the most important physiological correlates of BRS. They accounted for 52% of interindividual BRS variation. In addition, diastolic blood pressure and high-frequency component of heart rate variability were significant independent correlates of BRS. BRS was significantly higher in men than in women (15.0 +/- 1.2 vs. 10.2 +/- 1.1 ms/mmHg, respectively; P < 0.01). Twenty-four percent of women > 40 yr old and 18% of men > 60 yr old had markedly depressed BRS (< 3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthy subjects. In addition, we demonstrate that BRS values that have been proposed to be useful in identifying postinfarction patients at high risk of sudden death are frequently found in healthy subjects.