It has been reported that transforming growth factor (TGF)- β , which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), suppresses proliferation of alveolar epithelial cells in vitro. Although hyperplastic lesions of alveolar lining epithelial cells (ALECs) are characteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF- β , we searched for mutations in the microsatellite of the TGF- β receptor type II (T β RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the T β RII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle–like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low T β RII expression was confirmed by immunohistochemical staining. These data suggest that microsatellite instability in the T β RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.