Basic fibroblast growth factor (FGF-2) is involved in the development, maintenance, and survival of the nervous system. To study the physiological role of endogenous FGF-2 during peripheral nerve regeneration, we analyzed sciatic nerves of FGF-2-deleted mice by using morphometric, morphological, and immunocytochemical methods. Quantification of number and size of myelinated axons in intact sciatic nerves revealed no difference between wild-type and FGF-2 knock-out (ko) animals. One week after nerve crush, FGF-2 ko mice showed about five times more regenerated myelinated axons with increased myelin and axon diameter in comparison to wild-types close to the injury site. In addition, quantitative distribution of macrophages and collapsed myelin profiles suggested faster Wallerian degeneration in FGF-2-deleted mice close to the lesion site. Our results suggest that endogenous FGF-2 is crucially involved in the early phase of peripheral nerve regeneration possibly by regulation of Schwann cell differentiation.