The nonsteroidal antiinflammatory drug ibuprofen was tested as a potential agent in the pharmacological management of ischemia and reperfusion injury of swine flaps. After 6 hours of global ischemia, ibuprofen treatment was found to significantly improve the postischemic musculocutaneous flap survival. This was demonstrated by a dramatic 30.4 +/- 9.3% (p < or = 0.005) improvement in ischemic muscle survival, whereas the skin survival of ischemic musculocutaneous flaps was only moderately improved by 6.0 +/- 3.2% (p < or = 0.05). Thus, ibuprofen is potentially a powerful and effective treatment agent in the management of critically ischemic flaps and replants with high skeletal muscle content.