INTRODUCTION: Despite its potential, the validity of the flow-mediated dilation (FMD) test has been questioned because of lack of normalization to the vasodilatory stimulus. The hemodynamic conditions inside blood vessels lead to the development of superficial stress near the vessel walls, which can be divided into 2 categories: (1) circumferential stress (CS) and (2) shear stress (SS). Although SS is thought to be the primary governing stimulus, to the best of our knowledge, the degree to which CS contributes to FMD has not been reported in the literature. PURPOSE: The purpose of this study was to determine the importance of CS to FMD. We defined FMD as the SS-diameter dose-response slope. METHODS: Fourteen physically active, young [mean (SD) age, 26 (5) years], male subjects were tested. Progressive forearm heating and handgrip exercise elicited steady-state increases in shear rate. Hierarchical linear modeling was used to estimate change in diameter with repeated measures of SS and CS nested within each subject. RESULTS: Circumferential stress was found to positively promote FMD in addition to SS (β = 0.019, P = 0.019). However, the variance explained by CS was less than 1%. CONCLUSIONS: The physiologic significance of CS to FMD was minimal. However, physically active, young men were recruited; it remains to be determined whether CS has a more pronounced effect in subjects exhibiting cardiovascular risk factors.