The aim of this study was to investigate the effects of aging on hypotension in vivo and vasorelaxation in vitro induced by calcitonin gene-related peptide (CGRP), using young (3 months old) and elderly (20 and 28 months old) Sprague-Dawley rats. Vasorelaxant responses were measured in isolated rings of rat thoracic aorta and rat caudal artery, which show endothelium-dependent and endothelium-independent responses to CGRP, respectively. The CGRP-induced vasorelaxations were significantly diminished in 28-month-old male rats in both aorta (39.3% of responses in young controls at 10 nM CGRP) and caudal artery (28.5% of responses in young controls at 10 nM CGRP). Acetylcholine caused vasorelaxations in aortic rings of young male rats, but vasocontractions in aortic rings of 28-month-old male rats. Hypotension induced by CGRP was significantly diminished in both 20-month-old male rats (47.7% of young controls) and 20-month-old female rats (34.4% of young controls). Moreover, ovariectomy, known to decrease CGRP-induced hypotension in young female rats, did not further decrease hypotension to CGRP in elderly female rats. In conclusion, vasorelaxant responses in vitro and hypotensive responses in vivo induced by the neuropeptide CGRP are severely impaired in elderly rats as compared to young rats. The data suggest that the vasodilatory responses to CGRP in both large arteries and the small resistance-sized arteries regulating arterial blood pressure are damaged or down-regulated by the aging process.