The neointimal hyperplasia following a severe mechanical lesion of the rabbit thoracic aorta was studied by vital staining with Evans blue and transmission electron microscopy. Neointimal tissue covered with endothelium contained organized laminated elastin-rich commective tissue. On the contrary neointimal connective tissue covered with pseudoendothelium was disorganized, with a tendency to fibrosis. Reendothelialization, re-establishment of intimal barrier function and formation of lamellated neointimal connective were parallel events. The importance of a intact subendothelial zone controlling healing processes is discussed. Interaction of endothelium and smooth muscle cells seems to be essential in the regulation of neointimal tissue formation and is probably implicated in a general vascular reactive pattern.