Exposure to NO2 appears to affect lung defense mechanisms. We exposed rats to 10 ppm of NO2 for 24 h or 7 days and studied the production of tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) by alveolar macrophages after endotoxin stimulation. TNF and IL-6 production was significantly decreased (four-to sixfold) in the cell lysate of alveolar macrophages isolated from rats exposed to NO2. In parallel, PGE2 production was significantly increased in the same samples and in the bronchoalveolar lavage fluid. Northern blot analysis of the two cytokines indicated a reduction of the mRNA content. We also studied the expression of the TNF receptor type 1 (TNF-R1), known to neutralize TNF activity in its soluble form, and found that expression of the mRNA was increased after endotoxin stimulation. We can conclude that rats exposed to NO2 produce less TNF and IL-6 and that this might be related to increased PGE2 production and increased expression of TNF-R1.