Rat abdominal skin flaps were subjected to total venous occlusion for 8 h. Five minutes before release of the vascular occlusion, mannitol, mannitol plus anisodamin, anisodamin or placebo (0.9% normal saline) was administered intravenously. Drug treated flaps showed a statistically significant increase in the proportion of area surviving (P < 0.001). The combination of mannitol and anisodamin was not more effective than either agent alone in increasing the proportion of area surviving. The results of biochemical analyses indicated that neither mannitol nor anisodamin affected xanthine oxidase activity (p > 0.05) but that both agents significantly reduced the increase of malondialdehyde (MDA) concentration caused by ischaemia-reperfusion (p < 0.01). Treatment with mannitol or anisodamin also prevented the increase of lactate and water content and the decrease in glucose content in the island skin flap tissue which occurred on reperfusion. The data indicate that mannitol and/or anisodamin have the potential to salvage anticipated flap necrosis. It is possible that the mechanism of action is inhibition of damage caused by toxic oxygen species and improvement in capillary reperfusion.