We have previously demonstrated an acute inflammatory response and the production of tumor necrosis factor (TNF) in both guinea pigs and mice following a brief exposure to cotton dust. The role of TNF in the inflammatory response was studied using an antiserum to murine recombinant TNF raised in rabbits. Mice were administered anti-TNF antiserum on three occasions, with the last just prior to cotton dust exposure. Control animals received pre-immunization sera. Cotton dust exposure resulted in a 13 fold increase in inflammatory cell content of the bronchial alveolar lavage fluid. The predominant cell type was the polymorphonuclear leukocyte (PMN). Mice which had received the anti-TNF antiserum displayed a mild inflammatory response. These results suggest a role for TNF in the development of the acute inflammatory response which results from inhalation of cotton dust.