In conscious rats, infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) caused small, reversible reductions in hindquarters flow and vascular conductance only, whereas at a dose of 300 nmol/kg/min there was a tachycardia and an increase in mean arterial blood pressure, together with renal, mesenteric and hindquarters vasoconstrictions. Human alpha-CGRP (0.03 nmol/kg/min) caused tachycardia, hypotension, and transient renal, but sustained hindquarters, vasodilatation; these changes were accompanied by mesenteric vasoconstriction. Infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) during administration of human alpha-CGRP (0.03 nmol/kg/min) abolished the effects of the latter but these re-appeared when the human alpha-CGRP [8-37] infusion was stopped. This dose of human alpha-CGRP [8-37] did not affect cardiovascular responses to isoprenaline. These results indicate that human alpha-CGRP [8-37] is an effective antagonist of the cardiovascular actions of human alpha-CGRP in vivo.