In an intensive–care setting we studied the effects of ketoprofen, a dual inhibitor of cyclooxygenase and lipoxygenase, on circulatory and respiratory changes during established endotoxic shock in sheep. Two groups (n = 7 in each) were exposed toE. coliendotoxin, which caused a sharp increase in pulmonary artery pressure (200%; PAP), intrapulmonary shunt fraction (300%; Qs/QT%), and oxygen extraction ratio (50%; Vo2/ Do2%). There was also a significant decrease in mean arterial pressure (25%; MAP), respiratory compliance (60%; CT), arterial oxygen tension (65%; Pao2), and oxygen delivery index (15%; Do2) in both groups. After 30 min of endotoxin infusion, group K received ketoprofen, 2.5 mg/kg b.w. i.v., while group E served as shock controls. After 4 h there had been a significant improvement in MAP, Pao2, Do2, Qs/QT%, and CTin the ketoprofen–treated group compared with the controls (P<0.01). In addition, the oxygen extraction ratio normalised in group K, but remained 70–100% increased in group E (P<0.01). The wet–to–dry weight ratios of the lungs and the liver were significantly lower in the ketoprofen–treated group compared with the controls (P<0.05). It was concluded that ketoprofen significantly ameliorated the respiratory and circulatory effects of established endotoxic sho