During 1960-1966, research into pulmonary alveolar proteinosis crystallized the role of alveolar macrophages as central to surfactant turnover and alveolar cleanup, setting a macrophage-centered research agenda. Methodological breakthroughs enabled harvesting large numbers of alveolar macrophages and conducting reproducible functional studies of phagocytosis and surfactant processing, providing a platform for later PAP mechanistic work. The adoption of early bronchopulmonary lavage concepts in humans foreshadowed and catalyzed later therapeutic practices for alveolar clearance.