Amifostine is an organic thiophosphate compound, which has both cytoprotective and radioprotective effects. An experimental study was undertaken to investigate the effects of its use on reconstructive surgery in cancer treatment. One hundred and twenty guinea pigs were divided into three equal groups to investigate flap survival and healing, patency of microvascular anastomoses, and nerve regeneration, respectively. The groups were subdivided in such a way that they were given either preoperative or postoperative radiotherapy, with or without arnifostine treatment. Macroscopic and planimetric examination, light and electron microscopy, and histomorphometric analyses were performed to evaluate flap survival and healing, patency of arterial anastomoses, and nerve regeneration. Although flap survival rates were not affected, significantly better flap healing was observed in the postoperative radiotherapy subgroup with arnifostine treatment. However, arnifostine treatment did not result in a statistically significant difference in terms of anastornotic patency and nerve regeneration with either preoperative or postoperative radiotherapy. (C) 2004 Wiley-Liss, Inc.