The amplification of α-adrenoceptor-mediated vasoconstriction by angiotensin II was studied in femoral artery rings from rabbits. Threshold concentrations of angiotensin II (0.1 n M) increased the maximal response to clonidine to 139 ± 8% of control and produced a 3.2-fold increase in sensitivity. These effects of angiotensin II were reversed when tissues were pretreated with staurosporine (50 n M), an inhibitor of protein kinase C. The amplification of the α-adrenoceptor-mediated vasoconstrictor effects of thrombin and norepinephrine by angiotensin II were also reversed by pretreatment with staurosporine. Angiotensin II induced a response amplification in vascular smooth muscle known to be a nonspecific phenomenon, implying postreceptor interaction at intracellular transducer systems. Our findings suggest that upon activation of protein kinase C by angiotensin II, arterial responses to α-adrenoceptor agonists are amplified. This provides for nonspecific changes in vascular sensitivity by tonic alterations in postsynaptic modulation by enzyme systems known to regulate Ca<sup>2+</sup>-dependent phenomena, e.g. those related to vascular excitation-contraction mechanisms.