We examined the influence of untreated interstitial lung disease (ILD) on the in vitro release of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-Ira) from alveolar macrophages (AM); AM were harvested from normal volunteers, ILD patients, and patients with asbestos-related pleural disease but no ILD. AM were cultured for 24 h and assays for IL-1 beta and IL-1ra were done using sensitive and specific enzyme-linked immunosorbent assay. A greater amount of IL-1 beta was detected in AM supernatants from asbestosis, sarcoidosis, and IPF patients than in those from normal subjects. The IL-1 beta:IL-1ra ratio (IL-1 beta activity index [IL-1AI]) was significantly lower in supernatants of normal macrophages compared with macrophage supernatants from individuals with ILD. The IL-1AI correlated with bronchoalveolar lavage cellularity, a marker of disease activity. Current smoking was associated with lower IL-1 beta and IL-1ra release in ILD. The IL-1AI is a convenient method for comparison of IL-1 beta activity between patient populations.