The purposes of this study were to characterize the temporal relationship of distant organ dysfunction after mesenteric ischemia/reperfusion (I/R), and to ascertain if the neutrophil is critical to this process. Normal and neutrophil-depleted rats (vinblastine sulfate, 0.75 mg/kg intravenously) underwent 45 minutes of superior mesenteric artery occlusion and after 0, 6, and 18 hours of reperfusion, blood was sampled and liver and lungs were harvested. Iodine 125 albumin leak was used as a marker for pulmonary and liver injury, and serum acetoacetate/3-hydroxybutyrate (AcAc/3-OHB) was used as an index of hepatic mitochondrial redox state. Gut I/R at 6 hours increased 125I-albumin lung/blood ratio (gut I/R, 0.077 +/- 0.006; control, 0.045 +/- 0.004) and 125I-albumin liver/blood ratio (gut I/R, 0.120 +/- 0.007; control, 0.077 +/- 0.003), while AcAc/3-OHB decreased significantly (gut I/R, 0.420 +/- 0.040; control, 0.880 +/- 0.120). Neutrophil depletion eliminated these changes at 6 hours (blood AcAc/3-OHB, 0.720 +/- 0.100; 125I liver/blood, 0.068 +/- 0.006; 125I lung/blood, 0.046 +/- 0.007). We conclude the following: (1) intestinal I/R produces simultaneous liver and lung injury; (2) injury was present at 6 hours but is reversed at 18 hours; and (3) the I/R-induced liver and lung injuries were neutrophil mediated.