Injury to mammalian motor nerves can lead to paralysis, but relatively succul regeneration may occur when conditions are favorable. Elucidation of the mcanism upholding successful regeneration is of theoretical and clincal interest. In this study, the hypothesis that insulin-like growth factor H (IGF-ll) can stimulate motor nerve regeneration was tested. When IGF-H was infused continuously near a site of crush on the sciatic nerve, the distance of motor axon regeneration was increased snlfcantly in rats. In contrast, spontaneous regeneration was inhibited when an anti-IGF-H antiserum was infused through a "window" in the epineurium. Thus, infused IGF-il can increase, and endogenous IGFs can support, the regeneration of motor axons in lesioned nerves.Successful regeneration often is encountered following injury to the peripheral nervous system. Nevertheless, paralysis can result from injury to motor axons in nerves, particularly when lesions are in proximal nerve regions (closer to the spinal cord). Such paralysis might be reduced in incidence someday with improved understanding of the mechanisms supporting successful regeneration. The consequences of motor nerve injury continue to pose a serious medical, economic, and societal problem.The nerve distal to a site of injury contributes to spontaneous regeneration (1, 2). After transection, axons can cross a gap of several millimeters and enter the distal nerve stump, indicating the presence of soluble neurotrophic substances. Supporting cells in the nerve distal to a lesion indeed produce soluble factors, which attract and stimulate neurite growth (3)(4)(5). Freezing the distal nerve greatly reduces the population of Schwann, fibroblast, endothelial, and other cell types and impairs regeneration (6, 7). Motor (8)