We studied the lavage fluid recovered from a symptomatic patient with pulmonary alveolar proteinosis using in vitro assays for macrophage function. The alveolar macrophages from this patient had reduced phagocytic capacity. The particulate fraction from the cell-free lavage fluid (20,000 X gravity pellet) induced a pronounced phagocytic defect in normal mouse peritoneal macrophages but did not impair intracellular degradative activity. These results suggest that the lipoproteinaceous debris in patients with alveolar proteinosis can induce a phagocytic defect in alveolar macrophages, which probably increases the accumulation of more debris and may contribute to the increased risk of pulmonary infection.