We hypothesized that leukocytes contribute to decreased myocardial contractility following endotoxin infusion. To test this hypothesis, we administered endotoxin (1 mg/kg intravenously) to intact, anesthetized rabbits whose arterial blood perfused two isolated hearts at a constant pressure (75 mm Hg). One heart was perfused with blood passed through a leukocyte filter, whereas the other received unfiltered blood. Contractility of both hearts was measured every 30 min for 6 h, using the slope of the end-systolic pressure-volume relationship (Emax) and the maximum rate of change of intraventricular pressure (dP/dt(max)). In the unfiltered hearts at 6 h, Emax decreased to 81 +/- 6% (mean +/- SEM) of baseline (p < 0.05). In the hearts perfused with leukocyte-filtered blood there was no change in Emax. Similarly, dP/dt(max) decreased 74 +/- 9% of baseline in the hearts receiving unfiltered blood (p < 0.05) but did not decrease in the hearts receiving leukocyte-filtered blood. The leukocyte filter significantly reduced the number of neutrophils in perfusing blood (p < 0.01), decreased the number of neutrophils in the heart by 77% (p < 0.01), and decreased myocardial morphometric changes (p < 0.05). A 55 +/- 18% reduction in neutrophil L-selectin expression after endotoxin infusion (p < 0.01) suggests that the neutrophils were significantly activated. We conclude that leukocytes, notably activated neutrophils, may contribute to decreased myocardial contractility during septic shock.