Interleukin-1 (IL-1), a modulatory protein with immune and inflammatory functions, is spontaneously released by tissue macrophages in lower concentrations compared with peripheral blood monocytes. Conversely, in idiopathic pulmonary fibrosis, sarcoidosis, and certain inflammatory diseases, increased amounts of IL-1 are released by alveolar macrophages (AM). We examined IL-1 production by AM from patients with adult respiratory distress syndrome (ARDS) and compared it with that in patients with severe pneumonia requiring assisted ventilation, patients with pneumonia requiring parenteral antibiotics, and healthy control subjects. In vitro, ARDS AM released significantly more total IL-1 and IL-1 beta than did ARDS AM in patients with pneumonia and in control subjects. Moreover, after stimulation of these cells with 10 micrograms/ml of lipopolysaccharide (LPS), ARDS AM significantly increased release of IL-1 and IL-1 beta. AM from patients with severe pneumonia also released greater amounts of both IL-1 and IL-1 beta as fresh explants and after LPS stimulation when compared with control subjects. Incubation of AM with 250 U/ml human interferon-gamma (gamma IFN) was associated with less IL-1 beta release. However, stimulating AM from patients with ARDS and severe pneumonia with gamma IFN plus LPS enhanced the release of IL-1 beta compared with that in patients with pneumonia and in control subjects. ARDS AM released significantly more IL-1 beta than did all of the other groups. These results demonstrate that AM from patients with ARDS are capable of releasing significantly greater amounts of IL-1, which may be related to the progression of acute lung injury.