Neurons containing immunoreactivity to the endogenous lactose-binding lectin, RL-29, were examined in the L4 segment of the spinal cord of rats with an experimental neuropathy. The cells appeared by 5 days and were also present at 14 and 28 days postoperatively. All neurons were found in the dorsal horn ipsilateral to the injury. The neurons were multipolar and the reaction product revealed the morphology of the primary and secondary dendrites and some axons. Most of the neurons were located in the reticulated region of the dorsal horn, corresponding to Rexed's lamina V. In 14-day neuropathy animals treated with the NMDA-receptor antagonist MK-801, the number of RL-29 cell profiles observed was significantly reduced. Double labeling experiments revealed that spinothalamic tract neurons did not contain RL-29. The results suggest that the neuropathic injury produces a long term, transynaptic change in a subpopulation of dorsal horn neurons, that is mediated by excitatory amino acid transmitters acting at NMDA receptors.