Fibrosis, characterized by the accumulation of collagen, is a consequence of a chronic inflammatory response. The purpose of this study was to determine if tumor necrosis factor α (TNF-α), interleukin-1α (IL-1α) and IL-1β mRNA expression are altered acutely after irradiation, during the so-called "latent" phase of pulmonary injury, and to examine if these alterations persist through the development of pneumonitis and fibrosis. Further, we wished to determine if these changes differ between two strains of mice which vary in their sensitivity to radiation. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by slot blotting and hybridized with radiolabeled cDNA probes encoding for TNF-α, IL-1α and IL-1β. Autoradiographic data were quantified by video densitometry and results normalized to a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase. It was found that TNF-α mRNA levels were increased in C57BL/6 mice at days 1 and 7 postirradiation after 5 Gy and day 14 postirradiation after both 5 and 12.5 Gy, and IL-1α mRNA levels were increased in C57BL/6 mice at days 56, 112 and 182 postirradiation after both 5 and 12.5 Gy, and IL-1β mRNA levels in the C3H/HeJ mice were increased at days 56 and 182 postirradiation after 12.5 Gy. In summary, these studies demonstrated early and persistent alterations in TNF-α, IL-1α and IL-1β mRNA levels even at the lower dose (5 Gy). The temporal relationship between the elevation of these cytokines and the strain-dependent variation in fibrosis response suggests that IL-1α and TNF-α contribute to the radiation-induced component of pulmonary fibrosis, whereas IL-1β may have a protective function.