The rat sciatic nerve does not possess a high potential for regeneration through silastic tubes when the interstump nerve gap is greater than 10 mm. In this study, the effect of NGF treatment on regeneration of the rat sciatic nerve in 10- and 15-mm silastic chambers was compared. In addition, regeneration in 15-mm silastic chambers was compared to regeneration in 15-mm semipermeable chambers. Sections of tubing were implanted and filled with NGF or a control solution of cytochrome C (Cyt. C). Tube implants were removed at various postoperative times and regeneration was assessed histologically and behaviorally. NGF treatment promoted regeneration success rate. It enhanced the initial outgrowth of nonneuronal cells and neuronal fibers into the chamber producing more cellular, organized regenerates. At 2 weeks, in 10-mm chambers, NGF-treated regenerates had fourfold more unmyelinated fibers than controls. At 3 weeks, NGF-treated regenerates possessed threefold more myelinated fibers than controls. After 4 weeks all regenerates had similar numbers of myelinated nerves at the chamber's midpoint. This initial "head start" was sustained peripherally as indicated by the earlier return of sensory function (response to a noxious temperature stimulus) in NGF-treated animals. Finally, regeneration success rate in 15-mm semipermeable tubes is greater than that in 15-mm silastic chambers (NGF and Cyt. C). However, regenerates in silastic chambers possessed twofold more myelinated fibers than regenerates in semipermeable chambers. The positive effects of NGF on neural regeneration and recovery of sensory function provide support for the potential use of NGF in treating peripheral nerve injuries.