Although regular physical activity is associated with less hypertension and improved insulin sensitivity, there is debate regarding the role of insulin sensitivity in hypertension. Thus, in this cross-sectional study, the authors investigated whether physical activity and insulin sensitivity were associated with hypertension. The sample consisted of 1,599 persons aged 40-69 years who participated in the Insulin Resistance Atherosclerosis Study. The outcome measure was hypertension as measured by a standard protocol. Energy expended in vigorous physical activity was calculated from a recall interview on past-year physical activity. Descriptive statistics revealed that 590 (37%) participants had prevalent hypertension. In adjusted logistic regression analysis, participants expending >or=150 kcal/day in vigorous physical activity had an odds ratio for hypertension of 0.73 (95% confidence interval (CI): 0.55, 0.98) in comparison with participants who were sedentary. Further adjustment for insulin sensitivity resulted in attenuation of the effect of vigorous physical activity on hypertension (odds ratio = 0.97, 95% CI: 0.71, 1.33), while the effect of insulin sensitivity was significant (odds ratio = 0.33, 95% CI: 0.26, 0.41). These results suggest that longitudinal studies are warranted to determine whether insulin sensitivity is a mediator of the relation between physical activity and hypertension.