We compared the secondary ischemic tolerance of 8 x 12 cm surgically denervated pedicled island skin flaps and skin free flaps raised contralaterally on the buttocks of 50 pigs. The pedicled flaps and free flaps were subjected to 2 hours of primary warm global ischemia followed by 12 hours of reperfusion and 0, 2, 4, 6, or 10 hours of secondary warm global ischemia (n = 10 flaps). Skin necrosis was assessed 7 days after secondary ischemia. Pedicled skin flaps tolerated up to 10 hours of secondary ischemia without skin necrosis. However, incidences of skin necrosis (partial and total) in free flaps subjected to 0, 2, 4, 6, or 10 hours of secondary ischemia were 0, 10, 50, 80, and 100 percent, respectively. In a separate experiment, skin blood flow and hematology were studied in contralateral pedicled flaps and free flaps (n = 20) subjected to 4 hours of secondary ischemia. The skin blood flow measured by 15-micron microspheres at 1.5 hours of reperfusion was significantly higher (p < 0.01, n = 20) in pedicled skin flaps than in skin free flaps (1.91 +/- 0.35 versus 0.67 +/- 0.53 ml/min/100 gm). Under an operating microscope, microthrombi were observed near the arterial and/or venous anastomoses in 8 of 20 skin free flaps but none in the pedicled skin flaps. We obtained venous blood samples by cannulation of the major venae comitantes in 12 of the 20 skin free flaps in which there was no thrombosis in the vascular pedicle for hematologic studies. The venous plasma level of thromboxane B2 was significantly higher (p < 0.05) in the skin free flaps than in their contralateral pedicled skin flaps (195 +/- 49 versus 124 +/- 30 pg/ml). In addition, venous hematocrit, hemoglobin concentration, and white blood cell count also were significantly (p < 0.05) higher in skin free flaps compared with their contralateral pedicled skin flaps. Taken together, these observations were interpreted to indicate that buttock skin free flaps in the pig were less tolerant of secondary ischemia compared with their contralateral pedicled skin flaps subjected to the same ischemic protocol, and this reduced ischemic tolerance in skin free flaps was associated with compromised skin blood flow, hemoconcentration, and thrombosis in the vascular pedicle.