Calcitonin gene-related peptide (CGRP) is localized in nerve fibres in close association with the vasculature. The in vivo effect of human CGRP upon the cardiovascular system was investigated by intravenous infusion of CGRP into seven conscious sheep at doses of 1.5 and 10-pmol/kg per min for 75 min. CGRP at the 5- and 10-pmol/kg per min infusions decreased mean arterial pressure (maximal decrease of 10 mmHg) and stroke volume (maximal decrease of 42 ml/min), and increased heart rate by 60 beats/min. No changes in cardiac output were observed and total peripheral resistance only fell with the 5-pmol/kg per min infusion. Increases in both plasma arginine vasopressin and plasma renin concentration and a decrease in total and ionized plasma calcium were also observed. CGRP appears to be a potent vasodilator acting upon both arterioles and capacitance vessels in vivo.