BACKGROUND: Based on functional relations between the central autonomic network and cortical areas involved in motivational, attentional, affective, and executive function, autonomic regulation can mediate cognitive performance as well as cardiovascular and psychosomatic diseases. Our objective was to test the predictive value of resting heart rate variability (HRV), a measure of sympatho-vagal balance, with regard to the type and intensity of cardiovascular responses to mental challenge. MATERIALS AND METHODS: A total of 248 healthy subjects (85 females, aged 47.3+/-7.6 years; 163 males, aged 47.5+/-6.7 years) were included in the study. All participants underwent standardized psychometric testing (e.g., Stroop\'s color-word-conflict test). RESULTS: First, we found significant increases of heart rate and sympatho-vagal balance (low frequency/high frequency) and significant decreases of absolute LF- and HF-power in response to mental tasks. Second, there were significant differences in cardiovascular response to mental challenge when clustering our population on the basis of sympatho-vagal balance at rest. CONCLUSIONS: We conclude that short-term recordings of HRV can provide health-related information of cardio-vascular response to mental challenge. However, there is no association between sympatho-vagal balance at rest and classical cardiovascular risk factors.