The effect of sustained sympathetic nerve stimulation on autoregulation of blood flow was examined in the exteriorized cat sartorius muscle using intravital microscopy. Without sympathetic nerve stimulation (SNS), second-order arterioles showed insignificant dilation (3%) during arterial pressure reduction from 110 to 60 mmHg; volume flow fell coincident with pressure reduction. During SNS, these arterioles constricted significantly (25%), and their dilation during pressure reduction (20%) was significant and was significantly greater than that without SNS. Volume flow increased significantly (20-60%) during pressure reduction, a phenomenon termed superregulation of flow. Elevation of ambient oxygen in the suffusate from 0 to 20% caused arteriolar constriction but did not abolish arteriolar dilation during pressure reduction under sustained SNS. Arteriolar response to venous pressure elevation was also affected significantly by sustained SNS. Without SNS, third-order arterioles showed slight dilation (4%) when femoral venous pressure was elevated by 10 mmHg. During SNS, these arterioles constricted significantly and constricted further (20%) when venous pressure was elevated. Using a local anesthetic (lidocaine), we determined that a local venous-arteriolar reflex was not involved in the arteriolar constriction. Our data suggest that superregulation of flow during sustained sympathetic nerve stimulation is not due to metabolic factors but rather to an enhanced myogenic response.