Four groups of dogs were anesthetized, instrumented for measurement of blood pressures and flows across the liver, and, except for the control group, injected with 1 mg/kg endotoxin. The control group received only saline. One group received endotoxin only (ETOX) while animals in the other two groups received 10 mg/kg ibuprofen either 30 min before (PreIBU) or 30 min after endotoxin (PostIBU). Blood pressure, hepatic arterial and portal flow decreased after endotoxin injection in the ETOX and Post IBU animals but not in the PreIBU-injected animals. Pressure and flows returned to normal within 15 min after ibuprofen in the PostIBU animals but remained significantly lower in the ETOX animals. There was a transient increase in blood glucose concentration in the ETOX and PostIBU animals immediately after endotoxin injection, but not in the PreIBU group. Glucose then steadily decreased in all three experimental groups for the remainder of the experiment in spite of the fact that glucose production was elevated. Blood lactate and glycerol concentration increased in all three groups throughout the experiment. Ibuprofen was able to correct the pressure and flow changes caused by endotoxin, but did not prevent the hypoglycemia or accumulation of lactate and glycerol in plasma.