To evaluate the possibility that TGF-beta and TNF-alpha are involved in fibrosis induced in mouse lung by irradiation, the proportion of cells immunoreactive for each was compared in two strains of mice. C3HeB/FeJ mice develop only classical pneumonitis during the early phase, whereas C57L/J mice develop small, tightly packed areas of inflammation which undergo fibrosis during the latent period, and exhibit progressive fibrosis of large regions of intense inflammation during the early phase. Very few cells were immunoreactive for an antibody to the latency-associated peptide (LAP) of TGF-beta during the latent period in C3HeB/FeJ mice, and no cells were positive during the early phase. In contrast, between 0.7 and 10% of cells were positive in C57L/J mice in lesions without fibrosis and in lesions in the early stages of fibrosis. Fibroblasts positive for LAP were seen only in lesions containing fibrosis. A similar pattern of immunoreactivity was seen in C57L/J mice using an antibody which recognizes active TGF-beta, with the exception that positive fibroblasts were observed within areas of inflammation without fibrosis. Thus the association of active TGF-beta with fibroblasts might be a characteristic of the initiation of fibrosis in this model. TNF-alpha was detected in macrophages in all classes of lesions, and minor differences between the strains did not appear to be biologically meaningful.