In a previous study we found that the arteriolar myogenic response was enhanced during sympathetic nerve stimulation in the cat sartorius muscle. In this study we determined whether the enhancement was unique to sympathetic nerve stimulation. Changes of arteriolar diameter and red cell velocity during femoral arterial pressure reduction from 110 to 60 mmHg were examined. Arterioles of 40 microns diameter were constricted by norepinephrine infusion to a similar degree as sympathetic nerve stimulation. Arteriolar dilation to pressure reduction was significantly enhanced during norepinephrine infusion and was not significantly different from that during sympathetic nerve stimulation. This indicates that junctional release of transmitters is not essential and rules out prejunctional inhibition of neurotransmitter release during pressure reduction as a significant mechanism in the enhanced dilation. Arteriolar dilation to pressure reduction was also enhanced during vasopressin or BAY K 8644 (a calcium channel agonist) infusion. In all instances, autoregulation of flow was significantly enhanced. These results demonstrate that modulation of the myogenic response occurs at postreceptor sites in the smooth muscle cell.