Vasoactive intestinal polypeptide (VIP) contributes to the regulation of coronary vasomotor tone and circulating levels of VIP have been reported to increase during acute myocardial infarction. However, the changes in VIP concentration during exercise-induced ischemia have not been studied yet. Therefore, we sought to determine whether circulating levels of VIP change during treadmill exercise testing and whether they could be used as a marker of exercise-induced myocardial ischemia. Twenty-nine subjects with definitive positive (group-I) and 20 subjects (group-II) with negative results on treadmill exercise testing were included in this study. In order to assess circulating levels of VIP, blood samples were collected in both groups before exercise, at 5 minutes of exercise, at peak exercise, and at 10 minutes in the recovery period. There were Do differences between the two groups with respect to the baseline demographics of age, sex, heart rate, or blood pressure. The metabolic equivalents (METs) values, peak heart rate achieved, peak systolic-diastolic blood pressure, and exercise duration did not differ between the two groups. No significant differences were found in the circulating levels of VIP at any stage of the exercise between the two groups (10.5 +/- 2.5 versus 11.0 +/- 3.5 pmol/L, P = 0.5, 10.6 +/- 2.3 versus 10.6 +/- 3.3 pmol/L, P = 0.9, 10.9 +/- 3.1 versus 11.5 +/- 3.4 pmol/L, P = 0.5, and 10.7 +/- 1.8 versus 11.7 +/- 4.1 pmol/L, P = 0.3, respectively).