Calcitonin gene related peptide (CGRP) is known to be a potent microvascular dilator and hypotensive agent. This peptide and its receptors are distributed widely in both central and peripheral nervous systems. CGRP-containing neural fibers are closely associated with blood vessels in the arterial circulation where its release leads to vascular dilation. However, its role in cardiovascular regulation remains controversial. We studied the hemodynamic and autonomic function, as well as blood vessel structure in CGRP knockout (KO) mice. Blood pressure (BP), heart rate (HR) and activity level were assessed at least one week after mice were implanted with telemeters. Ten CGRP KO and ten wild type (WT) mice (4-5 month old) were used in this study. After the recording period, 24-hr urine and blood were collected for assessment of catecholamines and their metabolites. To study the baroreflex sensitivity, phenylephrine and sodium nitroprusside were administered in an acute study with seven mice from each group. We found no significant difference in 24-hr mean arterial pressure (MAP) (105.0 ± 1.8mmHg, vs. 112.1 ± 3.1mmHg, p= 0.05) between the two groups. There was also no difference in HR (KO: 566.4 ± 12.1; WT: 581.9 ± 8.5, p = 0.31). Norepinephrine was greatly elevated in both plasma and 24-hr urine in KO mice (in urine: KO: 956 ± 91 pg/ml, WT: 618 ± 46pg/ml, p = 0.004; in plasma: KO: 2505 ± 596pg/ml, n=6, WT: 1168 ± 98 pg/ml, p = 0.04). Paradoxically, cardiovagal baroreflex sensitivity was higher in the KO mice (KO: 3.2 ± 0.7 ms/mmHg, n=7, WT: 1.4 ± 0.3 ms/mmHg, n=7, p=0.03). Thoracic aortas were collected from both groups to measure vessel stiffness. The diameter at 125 mmHg of the aorta was significantly smaller in CGRP KO mice than in WT (321±30μm, vs. 422±82μm, p<0.01). Therefore, we hypothesize that although CGRP may have a limited contribution to physiological cardiovascular regulation, it may play a significant role in modulating the vagal tone and the structure properties of blood vessels.