Thirty years ago, John French wrote a seminal review describing the unique properties of the arterial intima. 1 His major point was that the smooth muscle cells of the intima have a unique morphology (Fig 1). French also pointed out that intimal formation appeared during normal development and aging as well as in the response of arteries to almost any imaginable injury, including atherosclerosis. This article attempts to update French's review. We will discuss the developmental origins of the intima and suggest that the arterial intima is a distinct tissue with a long and rapidly increasing list of differentially expressed genes (Table 1). This pattern of intimal gene expression may be responsible for the origins of atherosclerosis. The bulk of the review, however, deals with the posited role of smooth muscle replication in hypertension, atherosclerosis, and restenosis. Topics covered will include a revisiting of the 20-year-old observation that atherosclerosis is monoclonal2" 5 as well as reviews of current knowledge of the pharmacology of smooth muscle proliferation. Perhaps most important, however, we will present a critical discussion of evidence for and against a role for smooth muscle replication in these diseases.