THE endothelium is recognized as a major source of endothelin in the vasculature. In this report we show for the first time that endothelin can be demonstrated with immunoelectronmicroscopy in perivascular nerves. About 36% of the axon profiles (varicosity/intervaricosity) examined in the rat basilar artery showed immunolabelling with a polyclonal antibody to endothelin-1. Endothelin-labelled axon varicosities were characterized by the presence of small spherical agranular vesicles (42 ± 1 nm); some varicosities also contained large granular vesicles (++ ±5 nm) with labelled cores. Immunolabelling was mostly distributed in the axoplasm and in association with the membrane of synaptic vesicles (the lumen of the small agranular vesicles was immuno-negative). The presence of endothelin in perivascular nerves of the basilar artery suggests a neuronal as well as endothelial role in the physiological control of the vessel wall.