Adult retina ganglion cells regrow vigorously their lesioned axons in sciatic nerve segments transplanted at the site of optic nerve transection. In order to determine whether the transplanted peripheral nerve produces secretable substances involved in regeneration, a nerve exudate was collected from the adult sciatic nerve. Transection of the sciatic nerve in situ, implantation of silicone tubes around its proximal stump, and additional crush of the nerve further proximal permitted the reinnervation of the nerve stump inside the tube and the release of regeneration-induced substances. Biochemical analysis revealed that several proteins are secreted into the tubes. The fluid contents of the implanted tubes were removed 1 week after implantation and tested for neurotrophic activity in cultures of adult retinae. Massive regrowth of ganglion cell axons has been found in the presence of the nerve exudate. The numbers of axons were significantly higher than these obtained in the presence of nerve and fibroblast growth factors. The results suggest that the lesioned peripheral nerves deliberate during the period of reinnervation substances which also support axonal regrowth of injured central neurons.