This study investigates the role of prostaglandins (PG) in hyperdynamic sepsis. Thirteen chronically instrumented dogs were rendered septic by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. One day later, cardiac output (CO) increased from 280: t 0.22 to 3.72: t: 0.32 l/min (p= 0.011); heart rate (HR) increased from 122: 8 to 147: i: 6 beats/min (p= 0.005); mean pulmonary artery pressure (PAP) increased from 15: 1 to 19: 1 mmHg (p= 0.003); mean systemic arterial pressure (MAP) decreased from 120: t: 5 to 107: t: 7 mmHg; and systemic vascular resistance (SVR) decreased from 44.1: t: 2.6 to 29.3: t: 1.9 mmHg/l/min (p< 0.001). Sixty minutes after intravenous injection of indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), CO decreased to 2.60: t: 0.21 l/min (p< 0.001); HR decreased to 118: i: 5 beats/min (p< 0.001); PAP decreased to 17:: 1 mmHg (p= 0.021); and SVR increased to 43.7 mmHg/l/min (p< 0.001). In seven control dogs, laparotomy alone did not'significantly affect any of these parameters. Infusion of indomethacin caused a slight increase in MAP (106: 4 to 116 i: 4 mmHg, p= 0,035) but otherwise did not alter hemody-namics. It is concluded that administration of indomethacin or ibuprofen restores normal hemodynamics in a canine model of high-output sepsis, probably by inhibiting PG synthesis.