Sprouting from crush-injured rat sciatic nerves was studied by electron microscopy to clarify how regenerating sprouts are generated at the node of Ranvier and extended distally in the injured nerves. Three hours after injury, sprouting had already begun in a few nodes: part of the dense submembranous undercoat had disappeared from the nodal axolemma, and the axolemma was slightly evaginated where the undercoat was avoided. The sprout contained clear vesicles of about 50 nm in diameter in an amorphous axoplasm. In addition, vacuoles measuring 100-200 nm in diameter and multivesicular bodies were commonly found within or near these early sprouts. Six to 12 h after injury, nodes of Ranvier with sprouts increased in number in the region 1-1.5 mm proximal to the lesion. Sprouts grew toward the overlying Schwann cell basal lamina, and extended through the space between the basal lamina and Schwann cell plasmalemma (or myelin sheath). In the stem region continuous with the parent axon, regenerating sprouts displayed prominent neurofilaments, which were randomly arranged at 1 day post-injury, but oriented longitudinally by 5 days post-injury.