This study identifies a new role for the transcription regulator BACH2 in alveolar macrophage (AM) function and lung homeostasis. Bach2−/− mice were shown to develop pulmonary alveolar proteinosis-like disease, which comprised an accumulation of surfactants and infiltration of granulocytes and AMs in the lungs. Compared with wild-type AMs, Bach2−/− AMs showed increased uptake of surfactant lipids and impaired cholesterol metabolism, which contributed to a foamy appearance. Moreover, they had an altered expression of genes involved in chemotaxis (which probably contributed to the granulocyte infiltration) and showed a bias towards alternative M2 macrophage activation, which suggests that BACH2 normally limits M2 polarization. Importantly, the disease could be relieved by wild-type bone marrow transfer, which supports the key role for AMs in lung homeostasis.