The TNF is a monokine with cytotoxic and tumor-necrosing activities; in addition, TNF may play a role in inflammatory processes. The present study evaluates spontaneous and LPS-mediated release of TNF by AMs and autologous peripheral BMs of normal subjects and patients with pulmonary sarcoidosis. A recently developed cytotoxicity assay, specific for detection of TNF activity, was applied. This study demonstrates that (1) unstimulated mononuclear phagocytes released low levels of TNF with no differences between groups; (2) when effector cells were stimulated with LPS, AMs from patients with active pulmonary sarcoidosis released more TNF than AMs recovered from normal subjects and from patients with inactive disease; (3) this increase was compartmentalized to the lungs, since comparisons of TNF production by LPS-stimulated BMs failed to show any difference between study groups. These results suggest that TNF might play a role in the pathogenesis of the alveolitis of pulmonary sarcoidosis.