Twelve dogs were infused with 10(10) Escherichia coli/kg of body weight through a portal vein catheter over a 1-hour period; 6 dogs were treated with flunixin meglumine (1 mg/kg) 15 minutes after the infusion had begun. Six dogs (controls) were infused with a comparable volume of sterile saline solution over the same period. Over a 4-hour monitoring period, nontreated septicemic dogs developed systemic hypotension, decreased cardiac output, increased portal pressure, increased serum alanine transaminase values, increased extravascular liver water, increased liver glycogen depletion, and decreased arterial oxygen tension compared with control dogs. Accumulations of polymorphonuclear leukocytes and E coli were found in the livers and lungs of septicemic dogs. Flunixin meglumine treatment prevented systemic hypotension and hypoxemia, reversed the early but not the late stages of portal hypertension, and decreased E coli concentrations in the lungs. Other effects of treatment were not noticed.