A long-term objective of my laboratory has been to understand the mechanisms that regulate both normal and developmental growth of vascular smooth muscle as well as the accelerated growth of smooth muscle that occurs in atherosclerotic lesions or arteries of hypertensive patients and animals. Previous studies in this and other laboratories have demonstrated that smooth muscle cells are capable of two distinct growth responses in vivo, depending on the nature of the growth stimulus. Smooth muscle cell growth in large vessels of chronically hypertensive animals appears to occur primarily by enlargement of preexisting cells (i.e., cellular hypertrophy) with little or no cell proliferation (hyperplasia) and is accompanied by development of polyploidy in a large fraction of the cells. In contrast, in experimental injury models of atherogenesis, or after induction of severe acute hypertension, aortic smooth muscle cells undergo a classic proliferative response. This lecture focuses on possible control mechanisms for hypertrophy of vascular smooth muscle, with particular emphasis on examination of the possible role of contractile agonists as hypertrophic agents, exploration of how this process differs from cellular hyperplasia, discussion of the possible mechanisms for formation of polyploid cells, and examination of the role of mechanical factors in growth regulation of vascular smooth muscle cells.