In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress. Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 +/- 10 pmol/L to 752 +/- 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 +/-165 pmol/L (mean +/- SEM) and epinephrine by 218 +/- 76 pmol/L. During MST-2 the changes were 372 +/- 112 pmol/L and 187 +/- 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results. Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.