A number of noxious agents have been shown to affect the function and numbers of pulmonary alveolar macrophages. A protective factor which inhibits the lysis of alveolar macrophages was found in fluid lavaged from normal rabbit lungs. The protective action is lost following the in vitro and in vivo action of ozone. Dipalmitoyl lecithin exhibits a similar protective action, which is also lost following the in vitro action of ozone. The surface tension properties of the protective factor and dipalmitoyl lecithin may be altered, but not destroyed, following exposure to ozone. It is hypothesized that many environmental stresses, including ozone, may act by primary inhibition of a protective factor in lung fluid, which results secondarily in lysis of alveolar macrophages with loss of this defense mechanism of the lung against inhaled microorganisms and particulate matter.