Autonomic neuropathy involving the alimentary tract of several strains of inbred rats with chronic streptozotocin-induced diabetes has been characterized using ultrastructural methods. Markedly enlarged unmyelinated axons in the ileal mesentery of diabetic rats contain a variety of normal and unusual subcellular organelles similar to those described in experimental and clinical axonal dystrophies. These axonal alterations were seen after 6, 9, and 12 mo of diabetes, apparently increasing in frequency with time; lesions were absent, however, after only 3 1/2 mo of diabetes. An apparent proximo-distal gradient in the frequency of unmyelinated axonal lesions in this system suggests experimental diabetic autonomic neuropathy may represent an example of distal axonopathy. In addition, we have demonstrated an association of dystrophic axons with regenerative structures, including growth cones and clusters of filopodia.