Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease.