The effects of single or multiple inhalation exposures to ethylene dichloride (DCE) on the pulmonary defense systems of mice and rats were evaluated. Single exposures of mice to the threshold limit value of DCE (10 ppm) resulted in decreased pulmonary bactericidal activity to inhaled Klebsiella pneumoniae and increased mortality from Streptococcus zooepidemicus respiratory infection. A single exposure to 5 ppm DCE caused increased mortality from streptococcal pneumonia although bactericidal activity was not affected. Neither of these two parameters changed following single or five consecutive daily exposures to 2.5 ppm DCE. Single exposures to 10 or 100 ppm DCE did not affect mouse alveolar macrophage (AM) inhibition of the proliferation of a tumor target cell in vitro or AM in vitro phagocytosis of red blood cells. In rats, no effects were observed on pulmonary bactericidal activity. AM in vitro phagocytosis, AM cytostasis and cytolysis of tumor target cells, AM ectoenzymes, or blastogenesis of mitogen-stimulated rat T- and B-lymphocytes from lung-associated, mesenteric, and popliteal lymph nodes following single exposure to 100 or 200 ppm DCE or after twelve 5-hr exposures to 10, 20, 50, or 100 ppm DCE.