Our previous reports demonstrated the concomitant release of IL-1 beta and IL-1 inhibitory activity in the culture supernatants of BALF macrophages in both healthy subjects and patients with interstitial lung diseases. IL-1 inhibitory activities decreased in healthy smokers (HS), and patients with sarcoidosis (Sar), or idiopathic pulmonary fibrosis (IPF), compared with those in healthy nonsmokers (HNS), though an increase in IL-1 beta release was not detected. IL-1 inhibitory activity was mainly characterized as IL-1 receptor antagonist (IL-1ra). In this study, we confirmed a decrease in IL-1ra in terms of the amounts of protein (enzyme-linked immunoassay) and gene transcripts (reverse transcriptase polymerase chain reaction followed by high performance liquid chromatography). Imbalance between IL-1ra and IL-1 beta was expressed as a molar ratio of IL-1ra/IL-1 beta protein:(Sar; 4.20+/-2.06, IPF; 4.26+/-3.41, HS; 3.44+/-3.09 versus NS 8.33+/-2.77: P< 0.001). These results were similar in terms of the amounts of gene transcripts. In conclusion, the imbalance of IL-1 beta and IL-1ra production was confirmed at three levels: biological activity, amounts of protein, and gene transcript obtained from BALF macrophages in chronic inflammatory processes in the lungs.