There is evidence that long-term changes in the innervation of vascular smooth muscle alters the flow-stimulated release of vasoactive substances from the endothelium. To investigate the endothelial content of these substances following chronic sensory denervation, the distribution of endotheli-1 (ET-l), substance P (SP) and arginine vasopressin (AVP) in mature rat pulmonary artery endothelial cells was examined after neonatal treatment with the selective sensory neurotoxin, capsaicin. After immunolabelling with antibodies to the vasoactive peptides, Häutchen preparations of sheets of endothelial cells were observed and the percentage of immunopositive cells recorded. Preparations from capsaicin-treated rats displayed significantly more cells immunopositive to SP than controls (36%±3, n = 4 versus 9%±4, n = 4, P<0.01) and less cells immunopositive to ET-1 (36%±4, n = 4 versus 56%±3, n = 4, P<0.01). The distribution of vasopressin-immunopositive cells was unchanged by capsaicin treatment (10%±4, n = 4). Increased expression of SP and decreased expression of ET-1 in endothelial cells as a consequence of long-term sensory denervation may be a compensatory mechanism within the vessel to maintain an appropriate vascular tone.