To test the hypothesis that cytokines play a role in ischemic or reperfusion injury, we measured tumor necrosis factor (TNF) and interleukin-6 (IL-6) in pentobarbital-anesthetized dogs before, during, and after coronary occlusion lasting 60 min. Epicardial venous samples from the ischemic (IS) area were compared with nonischemic (NIS) and systemic (SYS) samples. Baseline IS TNF levels were low (2.2 +/- 1.2 U/ml) and not significantly different from NIS and SYS levels. After 50 min of coronary occlusion and at 40 min postreperfusion, IS, NIS, and SYS TNF levels were unchanged. At baseline, IS IL-6 levels were also relatively low (806 +/- 255 U/ml) and not significantly different from NIS and SYS IL-6. Although IS IL-6 increased significantly during coronary occlusion (5682 +/- 1495 U/ml) and reperfusion (10309 +/- 3708 U/ml), NIS and SYS levels were also elevated and did not differ significantly from IS values. The data indicate that TNF and IL-6 are not uniquely elevated in blood from ischemic or reperfused myocardium.