Objective: Pulmonary fibrosis is a prominent feature of chronic lung disease of prematurity (CLD), We sought to determine the influence of the potent profibrotic cytokine transforming growth factor beta-1 (TGF-beta(1)) on the development of CLD. Methods: We determined the concentration of active and total TGF-beta(1) in bronchoalveolar lavage fluid obtained from 18 infants who subsequently had CLD (mean gestation, 25.7 weeks; birth weight, 816 gm), 15 (29.8 weeks, 1493 gm) who recovered from the respiratory distress syndrome, and 7 (35.1 weeks, 2441 gm) control infants. Results: The concentration of both active and total TGF-beta(1) was increased in the infants with CLD when compared with the respiratory distress syndrome and control groups. The increase in active and total TGF-beta(1) was greatest on day 4 of age, when infants who eventually had CLD were compared with those who did not progress to CLD (active TGF-beta(1), 39.5 vs 4.6 ng/ml; total TGF-beta(1), 43.8 vs 13.8 ng/ml). In addition, immunocytochemistry studies localized pan-TGF-beta to alveolar macrophages obtained by bronchoalveolar lavage. Conclusions: These observations indicate that TGF-beta(1) may contribute to the fibrotic response that is observed in the lungs of infants who have CLD.