Two of the common features of inflammatory lung diseases are the increased production of pulmonary surfactant and the induction of lung cell apoptosis. However, the relationship between these two events has not been addressed. To investigate the role of surfactant in pulmonary inflammation and apoptosis, we instilled natural lung surfactant (Survanta) (1.6-12.5 mg) into the rat lungs and determined the number of alveolar macrophages (AMs) and apoptotic lung cells. High-dose treatments of Survanta (>6.25 mg/rat) caused an increase in macrophage cell influx and lung cell apoptosis at 4 weeks post-treatment. In vitro studies using lavaged macrophages showed Survanta did not cause apoptosis. We then examined the role of Survanta on ability of macrophages phagocytizing apoptotic cells. This study demonstrated that macrophages were able to eliminate apoptotic cells more efficiently in the absence of surfactant than in its presence. In vivo, high doses of Survanta decreased the ability to clear exogenously instilled apoptotic cells or bacteria. Taken together, our results suggest that excessive accumulation of lung surfactant by Survanta treatment can impair or overwhelm the phagocytic clearance function of AMs and that this impairment may lead to increased presence of apoptotic cells in the lung and bacterial survival.