In order to study the nephropathy associated with experimental streptozotocin diabetes, serila morphologic, ultrastructural, immunohistologic, and functional studies were done in diabetic Lewis rats to study the course of the nephropathy. Early in the course of diabetes, these animals developed an increase in mesangial matrix, with electron-dense material, IgG, and C3 in the mesangium. These alterations were progressive. Mesangial bars, proximal tubular vacuolization, and myeloid bodies were also present. Progressive increase in protein excretion and increase in creatinine clearance were observed. Hyperglycemia was accompanied by weight loss, persistent glycosuris, hyperphosphaturia, and hypercalcuria. Urinary glomerular basement membrane-like protein and major urinary protein were decreased. Normal age-matched controls showed no abnormalities. Some of the changes observed in diabetic rats are present in human diabetes.