Percutaneous transluminal angioplasty relieves discrete arterial stenosis but causes extensive vascular injury. There is denudation of the endothelium and variable medial disruption, but the effect on adventitial structures has not been studied in detail. We have investigated the innervation of the left and right carotid arteries after unilateral balloon-catheter-induced injury. Immunohistochemical examination of the arteries 1 day after Fogarty-catheter-induced injury of the left common carotid artery revealed a reduction in the density of protein gene product 9.5 (PGP)-, substance P (SP)- and calcitonin-gene-related peptide (CGRP)-containing nerves close to the medial smooth muscle of the injured vessel. At the same time, on the side contralateral to the injury, there was a substantial increase in the density of PGP-, SP- and CGRP-containing nerves innervating the carotid artery and vasa vasorum compared to controls. Immunoassay data from these vessels showed a selective increase in SP and CGRP contents of the contralateral carotid artery (SP, controls 0.02 ± 0.01, operated 0.59 ± 0.32 pmol/cm; CGRP, controls 0.03 ± 0.01, operated 0.14 ± 0.03 pmol/cm, n = 6, p& < 0.05). Neuropeptide Y levels were unchanged. Twenty-eight days after surgery, at which time a neointima was present, peptide levels were no different from controls, and the innervation of both the left and right carotid arteries and vasa vasorum was indistinguishable from the controls. In conclusion, balloon-catheter-induced injury includes damage to the perivascular nerves and induces a transient increase in the density of sensory neuropeptide-containing nerves innervating the contralateral, uninjured side. This novel observation may reflect neurocompensatory responses to vascular inj