The incidence and prevalence of diabetic neuropathies in Insulin Dependent (IDDM) and Non-Insulin Dependent (NIDDM) Diabetes Mellitus is not known because in previous studies the heterogeneity of diabetes and of the neuropathies was not taken into account, criteria for diagnosis and surveillance for neuropathy were variable, and studies were not prospective or population based. We have begun such prospective epidemiologic studies using a uniform algorithm for the classification of the diabetic disorders and uniform and validated approaches for the assessment of symptoms, neurologic deficits and various quantitative end-points of neural dysfunction. As regards cause, a key question which we are trying to answer is whether hyperglycemia and associated metabolic alterations affect neural tissue directly or whether there is an intervening tissue alteration between metabolic derangement and tissue change. Improved control of hyperglycemia does not appear to be associated with rapid neurologic improvement, possibly arguing for an intervening tissue alteration. The recently observed decrease in nerve oxygen tension and blood flow in streptozotocin diabetes suggests that an alteration of the nerve microenvironment may relate importantly to the cause of diabetic neuropathy.