BACKGROUND: Salt-sensitive normotensive men exhibit an enhanced pressor and heart rate (HR) response to mental stress. Stress-induced HR acceleration may result from sympathetic activation or vagal withdrawal. We studied the importance of vagal withdrawal for the increased stress responsiveness of salt-sensitive subjects. METHODS: We studied cardiovascular reactivity to mental challenge in 17 salt-sensitive healthy white male students and 56 salt-resistant control subjects who were comparable with respect to age, body mass index, and physical fitness. Salt sensitivity was determined by a 2-week dietary protocol (20 mmol v 240 mmol sodium/day). Mental stress was induced by a computerized information-processing task (manometer test). Electrocardiogram and finger blood pressure (BP; Finapres, Ohmeda, Louisville, CO) were registered continuously to determine HR and interbeat-interval length. Time and frequency domain (spectral power) based measures of respiratory-related heart rate variability (HRV) were calculated to estimate vagal cardiac control; diastolic BP reactivity was assessed to estimate peripheral sympathetic effects. RESULTS: Stress-induced increase in HR was higher in salt-sensitive than in salt-resistant subjects. Salt-sensitive subjects, in comparison to salt-resistant subjects, showed significantly reduced respiratory-related HRV during baseline and mental stress conditions (P <.01). The increase in diastolic BP during mental challenge was significantly greater in salt-sensitive subjects (P <.05). CONCLUSIONS: Our findings suggest reduced vagal and increased sympathetic tone during mental challenge in salt-sensitive subjects. Altered autonomic nervous system function may contribute to later development of hypertension in salt-sensitive individuals.