One month following induction of diabetes with streptozotocin one half of diabetic and control rats underwent unilateral nephrectomy. Subsequently, all animals were studied with respect to renal function and glomerular alterations of diabetes. Blood pressure levels were similar in all animals. Diabetic and control animals with unilateral nephrectomy had similar but elevated serum creatinine levels and lower creatinine clearance values as compared with the intact rats. However, on a per kidney basis the creatinine clearance levels were higher in the animals with unilateral nephrectomy. At both three and six months following nephrectomy, markedly increased mesangial matrix thickening and mesangial deposition of IgG and C3 were observed in diabetic rats with unilateral nephrectomy as compared with intact diabetic animals. Nephrectomy had no detectable effects on glomerular morphology or immunohistochemistry of nondiabetic rats. Thus, unilateral nephrectomy in the rat increases, at as early as three months, the severity of diabetic glomerular lesions.