Transection of the axonal process causes characteristic changes in the morphology and chemistry of the severed neuron. Such retrograde changes occur in both the extrinsic and the intrinsic neurons. There are, however, important quantitative and qualitative differences in the responses of these two classes of cells. Extrinsic neurons send their axons to the periphery and are in general capable of regeneration. They show alteration in their protein synthesis with an increase in structural proteins and a decrease in transmitter-related enzymes. Changes in certain RNA species may reflect the triggering of a genetically based “regeneration program.” A very early increase in glucose consumption is observed autoradiographically over the entire regenerating motor nucleus, suggesting participation of other tissue elements in the retrograde changes. Microglial cells and vascular cells seem to play an important role in this process too.