The fibrotic process of idiopathic pulmonary fibrosis (IPF) is considered to be the consequence of an exaggerated response to an inflammatory lung injury. In a previous report, except for the response to PG-E2, we found no difference in the proliferative profiles of lung fibroblasts between IPF patients and healthy subjects [Mio et al. (1992) Chest, 102:832-837]. In the present study, we hypothesized that lung fibroblasts from IPF patients would not undergo apoptosis as observed in the normal repair process. Additionally, we focused on the protooncogene bcl-2 which prevents apoptosis and the APO-1 (Fas antigen) which induces apoptosis. In order to explore this question, we used immunohistochemical staining to investigate whether apoptotic markers are expressed on lung parenchymal cells of IPF patients obtained by open lung biopsy. Bcl-2 protein was expressed on mononuclear cells in the mantle zone of lymphoid follicules and smooth muscle cells, but it was not expressed on other parenchymal cells. Apo-1 was expressed on epithelial cells, some germinal center cells, and many parenchymal cells including smooth muscle cells, fibrocytes, and myofibroblasts in patients with IPF, findings of which are fundamentally the same as those in normal subjects. Although we could not find any abnormality of lung fibroblasts in IPF patients, the positive staining with anti-Bcl-2 monoclonal antibody and anti-Fas (anti-APO-1) monoclonal antibody in lung lymphoid follicules suggests the continuous activation of B lymphocytes localized in the lung parenchyma in patients with IPF. The role of apoptosis in fibrosis should be further examined.