OBJECTIVES: We hypothesized that insulin sensitivity and vagal cardiac control are independently related in young men after adjustment for fitness and other confounding variables. DESIGN: Male volunteers aged 21-24 years with high (borderline hypertensive; n = 20) and low-normal (normotensive; n = 21) screening blood pressure (BP) were studied cross-sectionally. METHODS: Mean R-R interval (RR) and heart rate variability (HRV) were computed from 30-min ECGs, and baroreflex sensitivity (BRS) and latency (phase shift) from 15-min beat-to-beat finger blood pressure (BP) and heart rate recordings. Insulin-adjusted glucose disposal rate (GDR/I) was measured with a 90-min hyperinsulinaemic glucose clamp and fitness by peak oxygen uptake (VO2peak) during a treadmill test. RESULTS: HRV, baroreflex function, GDR/I, and VO2peak did not differ between the groups. GDR/I correlated positively with time and frequency domain HRV, including high-frequency power (HF) (r = 0.40, P = 0.01) and root-mean squared successive differences (RMSSD) (r = 0.43, P = 0.005), but not BRS or phase shift. GDR/I correlated with VO2peak (r = 0.70, P < 0.0001) and was explained (R = 0.56) by VO2peak (beta = 0.57, P < 0.0001) and RR (beta = 0.29, P = 0.03), independently of HRV and measures of obesity. Conversely, RR (beta = 0.55, P = 0.0004) and HRV, including HF (beta = 0.44, P = 0.006) and RMSSD (beta = 0.46, P = 0.004) were explained by GDR/I, independently of VO2peak. CONCLUSIONS: Insulin sensitivity and autonomic cardiac control are related independently of physical fitness in young men.