The interaction between skeletal muscle contraction and sympathetic nerve activation (SNA) on blood flow during exercise has remained ambiguous due to indirect estimates of vasomotor control. In the hamster retractor muscle (n=54), interactions between three levels of SNA (approximately 3, 6 and 12 Hz) and of contractile activity (2.5, 10 and 20 % duty cycle) were studied in feed arteries (FA) and first- (1A), second- (2A), and third-order (3A) arterioles using intravital microscopy. During functional dilatation with rhythmic muscle contractions, sympathetic vasoconstriction was sustained in FA and 1A but impaired in 2A and 3A (P<0.05), where vessels 'escaped' from responding to SNA. To account for changes in baseline diameter and blood flow during contractions, vasodilatation was induced passively (2-3 levels) in resting muscles with papaverine or sodium nitroprusside. Compared to functional dilatation, the range of passive dilatation was similar in 3A and progressively greater in 2A, 1A and FA. With passive dilatation, SNA responses were sustained in 2A and increased with baseline diameter in 3A. Blood flow through FA (rest, approximately 20 nl s(-1)) increased approximately 5-fold during contractile activity and approximately 10-fold during passive dilatation. Absolute flow reductions (nl s(-1)) with SNA increased during contractile activity and during passive dilatation; relative flow reductions were impaired during functional dilatation (P<0.05) and remained constant during passive dilatation. Thus, SNA can restrict blood flow to exercising muscle by constricting FA and 1A while dilatation prevails in 2A and 3A. Such concerted interaction will promote oxygen extraction when blood flow is restricted to maintain arterial pressure.