Serial renal morphologic, ultrastructural immunohisotlogic and functional studies were done on diabetic Lewis rats to evaluate the course of nephropathy and to study the effects of early pancreatic isografts on renal disease associated with streptozotocin diabetes. Three groups of experimental animals and one group of agematched controls were used. Group 1 consisted of 12 animals which were made diabetic with streptozotocin and which did not receive transplants. Early in the course of diabetes, these animals developed an increase in mesangial matrix, electron-dense material in themesangium, with immunoglobulin G, C3, and occasionally fibrinogen deposits in the glomerular mesangium. Alterations were progressive and mesangial bars, proximal tubular degeneration, tubular vacuolization, and myeloid figureswere present later. Progressive increase in protein excretion and increase in glomerular filtration rate were observed. Persistent glycosuria, hyperphosphaturia, andhypercalcuria. In contrast, only an occasional animal from Groups 2 and 3 with a pancreatic transplant showed renal in age-matched controls. These studies have demonstrated the evolution of renal glomerular and tubular changes in streptozotocin diabetic rats, and they have showed functional, and immunohistochemical changes.