This paper attempts to further delineate the similar pathobiologic mechanisms involved in the atherosclerosis and glomerulosclerosis processes. In particular, recent experimental data in models of both processes have focused on the roles of hypercholesterolemia and the monocyte/macrophage in propagating these lesions. In a nonimmune toxic glomerulopathy, chronic aminonucleoside nephrosis, our laboratory has demonstrated an important role for the glomerular macrophage, which is increased in number in temporal association with the onset of albuminuria, in propagating initial glomerular injury to glomerulosclerosis. In addition, a superimposition of dietary hypercholesterolemia further augments this heightened glomerular macrophage number and activates systemic macrophages. These data suggest a synergistic role between the hypercholesterolemia of nephrosis and the surge in glomerular macrophage number following initial glomerular injury in establishing a cascade of intercellular events that culminates in glomerulosclerosis. The intriguing histologic and immunohistochemical similarities between the evolving fatty streak in the atherosclerotic vessel wall and the progressive glomerular lesion leading to glomerulosclerosis suggest analogous pathobiologic mechanisms.