Tumor necrosis factor (TNF) is a monokine with cytotoxic and tumor-necrosing activities that may play a role in host defence against malignancies. The aim of the present study was to assess the ability of pulmonary alveolar macrophages (AMs) to release TNF. To accomplish this, a cytotoxicity assay specific for TNF detection was applied, using as targets actinomycin-D-pretreated WEHI 164 murine sarcoma cells. AMs mediated cytotoxicity levels comparable to those mediated by autologous blood monocytes (BMs). In addition, cytotoxicity was accounted for by a soluble factor released by effector cells and was completely inhibited by the addition of anti-TNF antibodies. These results indicate that AMs are able to release TNF. Moreover, since TNF has now been recognized as an important mediator of inflammation, its production by AMs suggests that this monokine might play a role in the pathogenesis of a variety of nonmalignant lung disorders.