Vascular smooth muscle from different arteries of the rabbit varies in sensitivity to norepinephrine, even when factors known to contribute to this variation are excluded. Sensitivity to norepinephrine mediated through the alpha-adrenoceptor is linearly related to the agonist dissociation constant, but is not significantly related to receptor reserve. These results suggest that agonist affinity is the primary determinant of sensitivity to norepinephrine, at least in these arteries, and that this is a locally regulated characteristic which may account for regional sensitivity changes.