We have investigated whether enhanced secretion of transforming growth factor-�� (TGF-��) by distal respiratory epithelial cells was associated with the development of bleomycin-induced pulmonary fibrosis. Type 2 pneumocyte-enriched preparations of bronchioloalveolar epithelial cells from normal mouse lung tissue released latent TGF-�� when cultured in serum-free medium. TGF-�� in culture supernatants could be detected using a sensitive enzyme immunoassay which employed enzyme complex amplification as a reporter system, as well as by a radiolabelled receptor competition assay. Exposure to bleomycin and other potentially fibrogenic stimuli in vitro did not stimulate production of TGF-�� by the epithelial cells but release was enhanced by treatment of the cells with interferon-��. Type 2 pneumocyte-enriched cell preparations obtained following induction of a pulmonary inflammatory response by administration of intratracheal bleomycin to susceptible C57BL/6 mice did not demonstrate increased release of TGF-�� in culture. However, the concentration of TGF-�� in bronchoalveolar lavage (BAL) fluids was significantly elevated compared to controls at 1 and 2 weeks after bleomycin-induced injury in these mice. No such increase was detected in BAL fluids from BALB/c mice, which are resistant to the effects of bleomycin. These results provide no support for a pathogenetic role of alveolar epithelial cell-derived TGF-�� in bleomycin-induced pulmonary fibrosis. Nevertheless, elevated levels of TGF-�� in BAL fluids may provide a marker of the progression of pulmonary injury to fibrosis. �� 1996 Blackwell Science Ltd.