Ozone (O-3), a major component of photochemical air pollution, is a strong oxidizing agent and highly toxic. Resident alveolar macrophages (AM) play an important immunomodulatory role in the lung via suppression of lymphocyte proliferation, thus limiting the magnitude and duration of local immune responses. Nitric oxide (NO) plays a crucial role in the immunosuppressive activity of AM, However, during immunoinflammatory responses, microenvironmental changes within the alveoli inhibit this AM function, permitting full expression of local T-cell-mediated immune responses. We hypothesize that similar changes in AM function may occur during inflammation induced by exposure to inorganic air pollutants, such as O-3. In order to test this hypothesis, in the present study, we investigated (1) whether O-3 exposure of rats might affect the immunosuppressive activity and NO production of bronchoalveolar lavage cells (BAL cells) and (2) whether changes in the microenvironment of the alveoli induced by O-3 exposure can affect the immunosuppressive activity and NO production of AM. AM-mediated immunosuppressive activity was measured as inhibition of concanavalin A (Con A)-induced proliferation of lymph node cells (LNC). Bronchoalveolar lavage was used to sample the alveolar microenvironment, and the resulting fluid (BALF) was tested for capacity to modulate AM activity in the cultures. BALF and BAL cells from rats exposed to 1 ppm O-3 or filtered air for 3 days were used. The present results demonstrate that BAL cells isolated from O-3-exposed rats suppressed Con A-induced LNC proliferation and produced NO in the same manner as BAL, cells (AM) from air-exposed rats, AM-mediated suppressive activity of LNC proliferation and NO production were markedly inhibited by BALE from O-3-exposed but not from air-exposed rats. These results suggested that AM-mediated immunosuppressive activity in vivo may be inhibited by the O-3-induced release of soluble factors which inhibit NO production by AM. (C) 1998 Society of Toxicology.