In a blinded study, 24 pigs were randomized to a 5-day preoperative treatment regimen of cyclophosphamide (n = 12) or placebo (n = 12). At operation, buttock cutaneous and latissimus dorsi myocutaneous flaps were created and then subjected to 6 hours of global ischemia. After 24 hours of reperfusion, flap skin and muscle survivals were determined. All cyclophosphamide-treated animals were rendered neutropenic (3 of peripheral blood). The results show that neutropenia had no effect on postischemic buttock cutaneous flap survival. In contrast, cyclophosphamide-induced neutropenia demonstrated a significant protective effect on postischemic latissimus dorsi myocutaneous flap survival. This study further implicates the neutrophil as a significant factor in the mediation of ischemia/reperfusion injury of myocutaneous flaps.