The role of neutrophils, their presence, and their degree of infiltration was examined in ischemic skin flaps. In a rat model, caudally based dorsal flaps were studied and neutrophils were manipulated by giving cyclosporine at two different doses (15 and 30 mg per kilogram), administrated either for 5 days as a pretreatment or 15 minutes before flap elevation. The presence of neutrophils and lymphocytes in both intravascular and extravascular space was assessed at 15, 30, and 60 minutes by skin biopsies, taken after elevation of the flap, by direct quantitative counting under the light microscope. The correlation between the counts and localization of the neutrophils, but not the lymphocytes, and the percentage of necrosis showed an early and definite role of neutrophils on skin flap survival during ischemic insult. Cyclosporine-treated flaps showed a 24% to 37% increase in viability when compared to control flaps. These data suggest that neutrophils, probably their interactions and/or products, play an important role in ischemic flap survival, and cyclosporine A is able to inhibit neutrophil accumulation and sequestration.