These data from in vitro studies, partially confirmed on intact glomeruli, suggest that glomerular cells are not only responsive to a number of growth-regulatory peptides but they are also important sources of several of these agents. The studies on transgenic mice confirm the potential role of the insulin-like peptides. This model also provides clear evidence that genetically directed modifications of cell behavior are important in the pathogenesis of glomerulosclerosis. The ability of glomerular cells to undergo proliferation and participate in hypertrophy of the glomerulus may be a critical determinant in the development of progressive glomerulosclerosis. That this ability is controlled by genetic differences between species and individuals seems well-established in both animal studies and clinical experience.