Activated T-lymphocytes play a central role in the alveolitis of pulmonary sarcoidosis by recruiting monocytes, the building blocks of granulomata, to the alveolar structures. The present study suggests that the lung mononuclear phagocyte population, which is derived from blood monocytes, may play a critical role in the pathogenesis of sarcoidosis by modulating local T-cell activation. In this regard, alveolar macrophages from sarcoid patients with high-intensity alveolitis released significantly greater amounts of lymphocyte-activating factor (interleukin-1), in vitro, than did macrophages from sarcoid patients with low-intensity alveolitis, patients with idiopathic pulmonary fibrosis, or normal control subjects (p less than 0.001, each comparison). Consistent with the concept that the lungs of sarcoid patients with low-intensity alveolitis may have a low level of inflammation present, alveolar macrophages from this group released more interleukin-1 than did macrophages from the normal group (p less than 0.05). These observations suggest that in pulmonary sarcoidosis: (1) mononuclear phagocytes are activated, and this state of activation correlates with the activity of the lung disease; (2) activated lung mononuclear phagocytes may modulate lung lymphocyte function, and thus play a critical role in the pathogenesis of this disease.