Cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to mediate host cell response to sepsis, trauma, and myocardial ischemia. We have previously found increased levels of IL-1 in the venous effluent during the reperfusion phase of skeletal muscle ischemia in a canine model. This study was done to evaluate whether TNF also played a role in skeletal muscle ischemia-reperfusion injury since IL-1 and TNF have inter-related functions. In twelve adult mongrel dogs (28-32 kg) one gracilis muscle was subjected to six hours of normothermic ischemia followed by normothermic reperfusion. The contralateral side served as a control and remained normally perfused throughout the experiment. Gracilis venous samples were collected at pre-ischemia and one hour of reperfusion. Systemic (arterial) blood samples were taken simultaneously with the venous samples at one hour of reperfusion. At the end of the experiment the muscles were harvested and amount of necrosis quantitated by serial transections, nitroblue tetrazolium staining and computerized planimetry. Muscle necrosis on the experimental side was found to be 48.86 +/- 5.37%. Sera were analyzed for TNF activity using a bioassay. TNF levels in the gracilis venous effluent at one hour of reperfusion were not significantly different from the simultaneous systemic (arterial) levels (27.15 +/- 5.05 pg/ml vs 18.23 +/- 4.27 pg/ml). Pre-ischemic levels of TNF were 96.50 +/- 20.12 pg/ml, which was significantly higher than either venous or arterial levels obtained after one hour of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)