Migration of smooth muscle cells (SMCs) of the media through the internal elastic lamina to the intima in response to various chemoattractants is considered to be an important event in the development of atherosclerosis. We evaluated the influence of elastin peptides prepared from normal aorta on migration of cultured rat aortic SMCs in vitro. Studies with filters coated with elastin peptides in a modified Boyden's chamber showed that the migratory response of cultured rat aortic SMCs in response to platelet-derived factors was impeded by filter-bound elastin peptides. The inhibitory effect appeared to be relatively specific for elastin peptides and for SMCs, as other matrix components (Types I, III, IV, and V collagens and fibronectin) did not impede SMC migration, and polymorphonuclear leukocytes were not impeded by elastin peptides. Elastin peptides in solution in the lower well caused the migratory response, and this response was also inhibited by filter-bound elastin peptides. Attractants such as platelet-derived factors and elastin peptides are likely to be present in the matrix around migrating SMCs. These studies suggest that elastin peptides adhering to the substratum or elastin, a major component of elastic fiber, may be one of the natural inhibitors of vascular SMC migration in response to chemoattractants in the fluid phase.