Autoradiographic and EM techniques were used to study the regenerative capacity of severed axons in the mammalian CNS. In infant and adult hamsters the pyramidal tract was severed unilaterally in the medulla several millimeters rostral to the decussation. After survival to adulthood, the animals received injections of [3H] proline in the sensorimotor cortex ipsilateral to the lesion. Autoradiography showed that labeled pyramidal tract axons in the medulla did not cross the lesion site. Instead, in animals with infant lesions there was massive new axonal growth arising from the severed pyramidal tract several millimeters rostral to the cut. Most of these labeled fibers crossed to the contralateral brainstem, coalesced into a compact bundle, descended just medial to the spinal trigeminal nucleus, and grew caudally for 6-7 mm. Although the trajectory of the regrowing axons was completely abnormal, their pattern of termination in the dorsal column nuclei and dorsal horn of the cervical spinal cord was normal. Synapse formation by the anomalous regrowing pyramidal tract axons in their appropriate terminal areas was confirmed by electron microscopy of terminal degeneration in animals with infant pyramidotomies followed by adult cortical lesions. Autoradiographic labeling of the new pathway at short postlesion survival times showed that the fibers grew out rapidly at about 1 mm/day, a rate somewhat slower than normal (2-4 mm/day). There was a dramatic difference in the capacity of the pyramidal axons to regrow in animals operated as infants vs. those operated as adults. The regrowth was maximal with lesions at 4-8 days of age. Capacity for new growth declined sharply thereafter such that after 20 days of age, pyramidal tract lesions elicited no new growth but instead a progressive axon degeneration retrograde to the lesion. These results, in contrast to many previous findings, show that significant regrowth of severed axons can occur in the neonatal CNS. Most importantly pyramidal tract fibers regrowing by anomalous routes can nevertheless establish synaptic connections in appropriate terminal areas and thus, as we show in the following paper, play a functional role in maintaining normal motor behavior.