INTRODUCTION Interleukin 27 (IL‑27) is a cytokine secreted mostly by antigen‑presenting cells. It is important for the immune polarization of T helper‑1 (Th1) cells, and its role in interstitial lung diseases (ILDs) and lung cancer has been investigated. OBJECTIVES We assessed IL‑27 expression in the lower airways of patients with selected ILDs and early‑stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS IL‑27 concentrations were examined by an enzyme‑linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid supernatants collected from patients with pulmonary sarcoidosis (PS; n = 30), extrinsic allergic alveolitis (EAA; n = 14), idiopathic pulmonary fibrosis (IPF; n = 12), nonspecific interstitial pneumonia (NSIP; n = 14), and NSCLC stages I to IIa (n = 16) with peripheral localization, and in controls (n = 14). The major lymphocyte subsets in BAL fluid were phenotyped, and intracellular IL‑27 expression was evaluated by flow cytometry. RESULTS IL‑27 concentrations in BAL fluid supernatants were significantly increased in Th1‑mediated conditions such as EAA and PS, but not in IPF or NSIP. The highest IL‑27 levels (median [SEM], 16.9 [17.5] pg/ml) were reported for NCSLC, and the lowest-for controls (median [SEM], 0.4 [0.2] pg/ml). IL‑27 was undetectable in corticosteroid‑treated patients with PS. Both CD4+ and CD8+ lymphocytes were positive for IL‑27; they were a possible local source of IL‑27 because the cytokine levels were positivelysignificantly correlated with the total number of lymphocytes, including CD4+ cells. CONCLUSIONS Our results support the Th1‑linked activity of IL‑27in ILDs. Early‑stageNSCLC is characterizedby high IL‑27expression in the lower airways. IL‑27 is produced by a high percentage of CD4+ and CD8+ cells in BAL fluid, both in patients and controls.