The present study examined release of TNF from guinea pig alveolar macrophages (AM) following inhalation of cotton dust. Guinea pigs were exposed for 6 hr to cotton dust and the lungs were lavaged a 0, 3, 6, 7.5 and 24 hr after the beginning of exposure. The results indicated release of TNF from AM upon cotton dust exposure and continued release of TNF from AM upon cotton dust expoculture of AM. The greatest amount of TNF release in both BAL fluid and in the AM supernatants occurred 3 hr into exposure. This peak TNF release corresponds with the onset of pulmonary function changes and neutrophil influx into the airways upon cotton dust exposure. These findings suggest that TNF may be important in initiation of pulmonary toxicity upon cotton dust exposure.