To investigate the systemic and hepatic reactivity to norepinephrine (NE) during chronic endotoxemia, we measured the reactivity of the drug in pigs infused with endotoxin (End, 160 ng/kg/min) during an 18-h period. At the end of the experiments, the hepatic vessels were removed to test the hepatic vascular reactivity in vitro. The pressive response to NE did not change over time in control (Ctrl) pigs, but endotoxin infusion decreased the response at t = 11 and 17 h. The reactivity of the portal vein blood flow did not change in Ctrl pigs but was significantly increased in End pigs at t = 5 h. Finally, endotoxin decreased the contractile response to NE only in transversal strips of portal veins isolated from End pigs. Thus, in this model, the decreased pressive response to NE develops over time, but the modifications of the hepatic vascular reactivity remain minor.