Although the distribution of atherosclerosis has been described, little is known about the direction of growth of plaques. In this study, 237 patients with slight or moderate atherosclerosis underwent femoral angiography twice at a 3-year interval, and the films were studied with computerized image analysis. First, atherosclerosis was measured as edge roughness, and the change in roughness of each 1-cm segment over the 3-year period was related to the edge roughness of the segments immediately upstream and downstream. On the medial side of the artery, the change in edge roughness was found to be more strongly related to the roughness values upstream than to those downstream of the segment studied. This suggests that growth in the downstream direction is more common than growth in the upstream direction. On the lateral side, more equivocal results were obtained. Atherosclerosis was also assessed by study of the cross-sectional area of the artery as a function of distance along the vessel. A mathematical model of plaque growth was formulated as a nonlinear filtering of this curve. Growth in the downstream direction was significantly (P<.001) more frequent than growth in the upstream direction. The findings are compatible with an atherogenic effect of fluid mechanical disturbances, such as flow separation, that may occur downstream of a stenosis.