The role of peroxynitrite generated from nitric oxide and superoxide anion was investigated in a model of acute inflammation induced by the injection of carrageenan into the rat hind paw. Paw edema was inhibited 8 h following the administration of carrageenan by N-iminoethyl-L-lysine (3-30 mg/kg, n = 6) or aminoguanidine (30-300 mg/kg, n = 6), two selective inhibitors of inducible nitric oxide synthase and by recombinant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (12 x 10(3) U/kg, n = 6, P < 0.001). Moreover, at the same time point following carrageenan administration, intense immunoreactive staining for nitrotyrosine (a marker of peroxynitrite formation) was detected. Our results suggest that the generation of nitric oxide, superoxide anion and peroxynitrite contributes to the edema observed in this acute model of inflammation.