Collagen sear formation at the cut end of a peripheral nerve, an important problem in clinical practice for neurosurgeons, obstructs sprouting of axons into appropriate distal fascicles, and thereby limits the regeneration process. Researchers have attempted to control collagen accumulation and neuroma formation with various physical and chemical methods, but with limited functional success. Recently, it has been demonstrated that transforming growth factor (TGF)-beta and basic fibroblast growth factor (bFGF) play an important role in collagen production by fibroblasts and in Schwann cell activity. In our study, rats were divided into a control group, a melatonin-treated group, a surgical pinealectomy group, and a group treated with melatonin following pinealectomy. They then underwent a surgical sciatic nerve transection and primary suture anastomosis. At 2 months after anastomosis, the animals were sacrificed and unilateral sciatic nerve specimens, including the anastomotic region, were removed and processed for immunohistochemical study from two animals in each group. For each antibody, immunoreactivity was assessed using a semiquantitative scoring system. Strong TGF-beta 1 and/ or bFGF expression was observed in the epineurium of animals that underwent pinealectomy, but no or weak staining was observed in animals in the control and melatonin treatment groups. Based on these data, we suggest that both TGF-beta 1 and bFGF have important roles in control of collagen accumulation and neuroma formation at the anastomotic site, and that the pineal neurohormone melatonin has a beneficial effect on nerve regeneration. (C) 2006 Elsevier Ltd. All rights reserved.