Abstract Bacterial pneumonia often complicates pulmonary congestive states. However, mechanisms by which interstitial and intra-alveolar fluid alter host responses to inhaled bacteria remain unclear. To study this problem, pulmonary edema was induced in mice with graded doses of purified α-naphthyl thiourea (ANTU), and in rats by surgical constriction of the abdominal aorta. In situ pulmonary bactericidal activity in individual animals was determined by quantitating the reduction of viable bacteria and radiolabel from aliquots of homogenized lungs 4 hours after aerosol challenge with radiophosphorus-tagged Staphylococcus aureus . Intrapulmonary antibacterial activity was depressed in both models of pulmonary edema and was related to the amount of intrapulmonary fluid accumulated. Hypoxia was not a factor in the aortic constriction experiments and the bactericidal defect in mice with ANTU-induced pulmonary edema was not reversed when animals were held in 60 per cent oxygen after exposure to the aerosolized bacteria. Impaired in vitro bactericidal activity of alveolar macrophages harvested from animals with ANTU-induced pulmonary edema was also demonstrated. It is concluded that pulmonary edema, pharmacologically induced with ANTU or surgically induced with aortic constriction, significantly impairs the antibacterial activity of alveolar macrophages.