After axotomy, changes in the compositon of fast axonally transported proteins (FTP) within the peripheral nervous system (PNS) axons were reported. The most significant and reproducible changes involved polypeptides found within the MW range of 31.0-14.5 kilodaltons. Whether similar changes following axotomy occur in axons of the CNS was determined. Intracranial axotomy of the left optic tract was performed stereotaxically in rats. Six days post axotomy 50 .mu.Ci35[S]-methionine was injected into the vitreous body of both eyes. FTP were isolated within the optic nerves 2 h after isotope injection. The nerve segments were processed for SDS-PAGE [sodium dodecyl sulfate polyacrylamide gel electrophoresis] fluorography and compared to similarly prepared fluorographs of normal and 8 day post axotomy sciatic nerve segments. The labeling of 5 major polypeptide bands (S1, MW .simeq. 28,000; S2a, MW .simeq. 25,000; S2b, MW .simeq. 23,000; T1, MW .simeq. 20,200; and T2, MW .simeq. 17,000) was studied by laser densitometry. Band S2b showed a highly significant (P < 0.001) increase in concentration, while bands S1 and T1 demonstrated highly significant decreases in concentration following axotomy of the sciatic nerve. After axotomy of the retinal ganglion cell axons the only significant change was a decrease (P < 0.05) in T1. Failure of CNS axons to respond similarly to PNS axons following axotomy may be related to the failure of CNS axons to regenerate.