There is a well established connection between hyperinsulinemia and hypertension, and activation of the sympathetic nervous system (SNS) by insulin has been proposed as one mechanism. In short term infusion studies, hyperinsulinemia during the euglycemic glucose clamp examination is associated with increased norepinephrine concentration. However, many of the studies lack sufficient control groups. The euglycemic glucose clamp examination could possibly, by discomfort from iv cannulas, the use of heating cuffs, and prolonged immobilization, by itself increase SNS activity. To examine this, we included nine controls, who had saline instead of glucose and insulin infused iv, among other healthy young men (n = 50) who underwent the euglycemic hyperinsulinemic glucose clamp. During hyperinsulinemic clamp, the plasma norepinephrine concentration increased from 0.87 +/- 0.06 to 1.06 +/- 0.05 nmol/L; in the control study, it increased from 0.99 +/- 0.14 to 1.21 +/- 0.11 nmol/L, a significant treatment effect (P < 0.001, by repeated measures analysis of variance), but no group x treatment effect (P = 0.17), i.e. there was no difference between the groups. There were no significant changes in systolic or diastolic blood pressure, heart rate, or plasma epinephrine concentration during the clamps, nor any differences between the groups. We conclude that the increase in plasma norepinephrine concentration observed during an euglycemic glucose clamp examination may be attributed to the procedure itself, and that the inclusion of a control group is mandatory when assessing SNS activity.