Rat mesenteric resistance blood vessels are innervated by nonadrenergic, noncholinergic (NANC) vasodilator nerves. In vitro pharmacological, biological and immunohistochemical studies have provided evidence that the calcitonin gene related peptide (CGRP), a 37 amino acid peptide translated by the calcitonin gene, has a potent vasodilator effect and acts as a vasodilator neurotransmitter for NANC vasodilator nerves. The CGRP-containing vasodilator nerves inhibit adrenergic nerve-mediated vasoconstriction through direct relaxation of vascular smooth muscle, while adrenergic nerves suppress the neurotransmission of CGRP-containing nerves by inhibiting CGRP release from the nerve. Thus, CGRP-containing nerves and adrenergic nerves control vascular tone with reciprocal interferrences. In in vivo studies, spinal cord (T9-12) stimulation of pithed rats produced a NANC depressor response mediated by endogenous CGRP, suggesting that CGRP-containing nerves are regulated by the central nervous system. The malfunction of CGRP-containing vasodilator nerves may be involved in cardiovascular diseases such as essential hypertension, coronal vasospasm, cerebral vasospasm and Renaud's phenomenon. It is suggested that the CGRP-containing vasodilator nerves play an important role in the regulation of vascular tone.