Functional and structural neuropathy was examined in hyperglycemic (diabetic) BB rats maintained on small maintenance doses of insulin, hyperglycemic BB rats receiving no insulin, and BB rats in whom hypoglycemia was induced by the administration of excessive insulin doses. The data were compared with those of non-diabetic age- and sex-matched BB rats. Functional deficits and structural abnormalities were comparable in diabetic rats with and without insulin supplementation, suggesting that the generally necessary insulin dosing in this model does not per se account for the neuropathy. Hypoglycemic neuropathy was characterized by slowing of nerve conduction velocity, marked loss of anterior horn motoneurons and Wallerian degeneration, as well as loss of large myelinated fibers, suggesting a neuropathy involving predominantly motoneurons. Diabetic neuropathy was not associated with nerve cell loss but showed marked axonal atrophy involving predominantly sensory fibers. Thus, diabetic and hypoglycemic neuropathies are two distinguishable entities under strict experimental conditions, but may overlap in human diabetic subjects in whom tight insulin control is desirable.