Sepsis/septic shock and multiple organ failure are important causes of morbidity and mortality. Our objective was to study sepsis and organ failure in a fluid-resuscitated septic model. Male SD rats were anesthetized with halothane, the jugular vein catheterized, and CLP performed. Each rat was maintained in a metabolism cage on continuous intravenous fluid (3 mL/h/rat). Urine rate and [creatinine] urine were measured daily. At day 5, serum creatinine with chemistry profile, complete blood count, clotting times, and wet lung/body weight ratios were also measured. Glomerular filtration rate (GFR) was measured according to the principle of endogenous creatinine clearance. GFR was correlated with the product of urine rate [creatinine] urine (R=. 79), so that product was used as a daily indicator of GFR. Urine output remained> normal during sepsis. Heparin and antithrombin III were tested in this model. The model was associated with 40% mortality, a 60% reduction in platelet count, liver damage, a 75% reduction in renal function, muscle damage, and a normal wet lung/body weight ratio. Treatment with heparin/anti-thrombin III ameliorated the decrease in GFR (p<. 05) observed in the nontreated animals, prevented the septic-induced thrombocytopenia (p<. 05), and improved survival (p=. 05).