Pulmonary alveolar proteinosis is characterized by the accumulation of a lipoproteinaceous material within the alveoli of the lung. It is well established that patients with pulmonary alveolar proteinosis have a high incidence of complicating pulmonary infections possibly resulting from defects of antibacterial functions of alveolar macrophages. Moreover, for unclear reasons, an inflammatory response in the airways is frequently absent. In order to investigate the role of the lipoproteinaceous material in these two patterns, we tested the in vitro effects of a lavage fluid from a human pulmonary alveolar proteinosis on the secretion of reactive oxygen intermediates and arachidonic acid metabolites by normal guinea pig alveolar macrophages. After incubation with the lipoproteinaceous material, the luminol-enhanced chemiluminescence of zymosan-triggered alveolar macrophages was reduced in a dose-dependent fashion. The lipoproteinaceous material similarly reduced the chemiluminescence response in a cell-free xanthine-xanthine oxidase system generating superoxide anions. This latter observation suggests that the lipoproteinaceous material acts as a scavenger for superoxide anions produced by alveolar macrophages. Its purified protein or phospholipid fractions also resulted in a general inhibition of the secretion of arachidonic acid metabolites by alveolar macrophages challenged in vitro with zymosan. Our results suggest that the alveolar filling material of pulmonary alveolar proteinosis may inhibit the action of antibacterial and/or proinflammatory agents produced by alveolar macrophages. We speculate that such effects of the lipoproteinaceous material may play a role in vivo in the high incidence of pulmonary infections and in the absence of discernible interstitial or intraalveolar inflammation seen in pulmonary alveolar proteinosis.