The distribution of Endothelin-1 (ET-1), a potent vasoactive peptide, within endothelium of human atherosclerotic arteries was examined using a novel en face immunohistochemical technique. The vast majority of endothelial cells were immunoreactive for ET-1. Staining intensity was increased in areas overlying atherosclerotic plaques, calcified media, fatty streaks and about flow dividers, compared with adjacent regions. Multinucleated 'giant' endothelial cells were more common in regions containing strong ET-1 staining than elsewhere. Clusters of leucocytes (probably monocytes) were frequently observed adhering to the endothelial monolayer but not neighbouring regions of denudation. Occasionally underlying macrophage/foam cells and smooth muscle cells were exposed to the surface and included in the en face (Häutchen) preparation. Smooth muscle cells did not stain for ET-1 while macrophages and the larger foam cells were positive for ET-1. These results support the hypothesis that expression of ET-1, at sites containing atheromatous disease, may be involved in the development of atherosclerosis.