In this review we have tried to identify the characteristic features of SMCs in developing lesions of atherosclerosis and the extracellular factors that may be involved in regulating these altered features. Though the list seems long and complex there is probably a great deal of interplay among the different regulatory mechanisms. The function and activities of SMCs in the artery are dependent on the milieu created by the surrounding cells and the components of the extracellular matrix. In the normal, uninjured media of the artery, SMC phenotype and function seem to be in large part determined by the extracellular matrix in which they are embedded and by diffusible factors, in particular from endothelial cells. Endothelial cell injury, infiltration of monocytes and lymphocytes, and ultimately, thrombosis and platelet release, as seen in developing lesions of atherosclerosis, dramatically alter the balance of growth-regulatory and vasoactive factors present in the local environment. These extracellular factors (table and figure) can alter both SMC phenotype, and thus responsiveness, and SMC migration, proliferation, and synthesis of the extracellular matrix. A better understanding of how specific factors mediate these responses, should make it possible to determine the ways in which the SMC response can be modulated. Though growth regulatory molecules seem to be key to this process, the challenge for the future is to understand their regulation in the environment of the artery wall and the interplay between growth-regulatory molecules, extracellular matrix, and vasoactive agents.