Optic nerve section in the newborn rat results in a rapid apoptotic degeneration of most axotomized retinal ganglion cells (RGCs). This massive process of neuronal death has been ascribed mainly to the interruption of a trophic factor supply from target structures rather than to the axonal damage per se. To distinguish between these two possibilities, we induced a reversible axonal transport blockade in the developing optic nerve by topical application of a local anesthetic (lidocaine). Light and electron microscopy showed no alterations in the fine structure of treated optic nerves. Retinae of treated and control rats were stained with cresyl violet and examined at different times after surgery. We found that axonal transport blockade induced only a limited number of pyknotic RGCs. Degeneration of these cells was completely prevented by inhibiting protein synthesis during lidocaine application. We conclude that the rapid degeneration of RGCs after axotomy can be ascribed only partly to the loss of retrogradely transported trophic factors.