The effect of sustained insulin-induced hypoglycemia on peripheral nerve function and structure was examined in rats. After a period of hypoglycemia (less than 2.5 mmol/L) of at least 72 h, axonal degeneration and reduction of the maximal amplitude of the evoked muscle action potential occurred, the two abnormalities being correlated negatively (r = -0.99, 2P = 0.00097). One of five rats developed paresis of both hindlegs as well as nerve damage and perikaryal alterations of lower motor neurons.