Kidneys of patients with severe diabetic nephropathy demonstrate marked linear immunofluorescent staining of extracellular membranes, including the tubular and glomerular basement membranes (TBM and GBM) and Bowman's capsule. Immunofluorescent studies were carried out on kidney tissue obtained from 12 diabetic and 17 nondiabetic patients from two to 12 years following renal transplantation. The frequency and intensity of SgG and albumin staining of these membranes were significantly greater in the diabetic than in the nondiabetic patients (P less than 0.0005). TBM, GBM, and Bowman's capsule staining did not occur in any of the seven kidneys studies at the time of their transplantation into diabetic recipients. Thus, the abnormalities leading to the deposition or trapping of proteins in renal extracellular membranes occur early after the placement of normal kidneys into the abnormal metabolic environment of the diabetic transplant recipient. The present study supports the concept that basement membrane alterations in diabetes are a consequence of the biochemical perturbations of diabetes rather than a separately inherited genetically linked disorder.