The effect of reactive oxygen generation on intact livers was studied. Production of reactive oxygen species in perfused livers isolated from normal and endotoxin-treated rats was measured using chemically enhanced chemiluminescence. The resting state chemiluminescence of the livers increased on endotoxin administration and was maximal about 6 h after treatment. Chemiluminescence from the livers was further stimulated severalfold by inclusion of phorbol myristate acetate in the perfusion medium, reaching maximum intensity 3 h after endotoxin treatment. Oxygen consumption by the endotoxin-treated liver showed a transient increase followed by a significant decrease on phorbol myristate acetate stimulation, which was inhibited by dexamethasone. These results are consistent with the occurrence of a respiratory burst followed by oxygen-radical-species-induced vasoconstriction in the intact perfused liver. The evaluation of reactive oxygen species by resident and accumulated macrophages in the intact liver is made possible by these studies, and related effects on the liver could be conveniently and quantitatively followed using this model.