The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic agent vincristine sulfate (VCR) has hampered the correlation between experimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR total dosage similar to that used in humans, a peripheral polyneuropathy characterized by electrophysiological changes that overlap those observed in the clinical setting. The present study was aimed at investigating the ultrastructural features of 3 different nerves (sural, peroneal, and medial gastrocnemius) in rabbits treated with 3 VCR doses that fall within the range (0.2-0.3 mg/kg i.v.) known to be efficacious chemotherapeutically and active neurotoxicologically. Regardless of the dose and the nerve under examination, histopathologic alterations appeared in the form of an overall loss of myelinated fibers, accompanied by successful attempts of regeneration and remyelination. Fibers undergoing Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a consequence of ingrowing Schwann cell processes from the adaxonal surface. These ingrowths tended to isolate axoplasmic areas, retaining a fairly normal structure from other areas already crowded with altered organelles and cytoskeletal elements. In any event, neurofibrillary accumulations were rarely seen. These patterns are discussed with reference to those reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripheral neuropathy.