Reactive oxygen intermediates such as free radicals have been proposed to mediate lung injury. The present work examined whether or not enzymatically generated oxygen metabolites altered serotonin clearance. Isolated, plasma-perfused rat lungs were exposed to xanthine oxidase (XO) and hypoxanthine (HX). Pulmonary arterial pressure (Ppa) and lung weight were recorded. Fulminant edema was defined as a spontaneous weight increase exceeding 500 mg. Inactivation of serotonin was determined by superfusion bioassay. XO and HX reduced serotonin inactivation from 74 +/- 3% (mean +/- SEM) to 62 +/- 2%. This reduction was inhibited by the scavenger enzymes superoxide dismutase (SOD) and catalase and by allopurinol, an inhibitor of XO. Hydrostatic edema and perfusion per se did not decrease the pulmonary clearance of serotonin. XO and HX did not significantly alter Ppa. Fulminant edema developed in four of six lungs after exposure to XO and HX compared with none in the other groups. It was concluded that reactive oxygen intermediates inhibited serotonin inactivation in isolated rat lungs.