We have used a previously described model of bilateral radiation-induced lung disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the role of hyaluronan in this process. Hyaluronan was measured in the bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma irradiation or sham irradiation. Four weeks after irradiation, during peak alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was in the intra-alveolar edema fluid but was not increased in the alveolar walls; hyaluronan, measured by high-performance liquid chromatography, also was not elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis (6 to 20 weeks). The administration of methylprednisolone significantly decreased the alveolitis, including the increase in hyaluronan in the alveolar space and serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of inflammation and cannot be used as a serum marker to predict the onset of radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does not appear to be a necessary precursor in the evolution of radiation fibrosis.