The distribution of nerves with vasoactive intestinal peptide (VIP)-like immunoreactivity has been examined in the heart and vascular system of guinea-pigs. There was a very sparse supply of fibres to the heart. No immunoreactive cell bodies were found in the intrinsic cardiac ganglia; however, positive nerve cell bodies were seen along the superior vena cava near the right atrium. There were immunoreactive fibres with most arteries; these fibres were located at the media-adventitia junction. The supply to major distributing arteries, such as the aorta, subclavian, carotid and femoral arteries as well as to the pulmonary arteries, was sparse. Of the individual vascular beds, the most densely supplied arteries were the mesenteric and uterine (or in the male deferential) arteries. Arteries running to other organs or tissues, such as skeletal muscle, kidney, pancreas, spleen and heart were less densely supplied. There were clear differences in the innervation of different cerebral vessels. The greatest density was associated with the anterior and middle cerebral arteries. Fewer nerves accompanied the posterior cerebral, cerebellar and meningeal arteries. There was a sparse innervation of the rostral part of the basilar artery. Throughout the body, veins were sparsely supplied. The distribution of nerves with VIP-like immunoreactivity was not changed when noradrenergic nerves were degenerated by 6-hydroxydopamine or when substance P nerves were disrupted by capsaicin. It is concluded that VIP containing nerves innervating the heart and blood vessels form a population distinct from the substance P-containing and the noradrenergic nerves. It is suggested that the VIP fibres might be efferent vasodilator nerves to the blood vessels.