Changes in gene expression were investigated in axotomized CNS neurons under conditions that inhibit or permit regrowth of their damaged axons. Levels of mRNA encoding beta-tubulin, the 150 kDa neurofilament subunit (NF-M), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were examined by quantitative in situ hybridization of adult rat retinal ganglion cells (RGCs) after axotomy in the optic nerve or during regeneration in a peripheral nerve (PN) graft. Soon after optic nerve section beta-tubulin, NF-M, and GAPDH mRNA levels decreased and remained low during the 1 month studied. In these retinas beta-tubulin mRNA fell to approximately 50% of normal controls. However, in the PN-grafted retinas, where approximately 20% of the surviving axotomized RGCs regenerate their axons, there were "hot spots" of beta-tubulin mRNAs where neuronal levels were nearly 300% higher than in controls. By retrograde neuronal labeling these hot spots were shown to correspond to the injured RGCs that regrew their axons into the PN graft; beta-tubulin mRNA levels in nonregenerating RGCs of the same retinas averaged 63% of controls. We suggest that interactions of RBC axons and components of the grafts' non-neuronal environment play a key role in the over fourfold differences in beta-tubulin mRNA levels observed between injured and regenerating RGCs.