There has been a long-standing controversy of whether megakaryocytes release platelets in the marrow or travel to the lungs and release platelets there. Using two-photon electron microscopy and orthotopic lung transplantation, Lefrançais et al. now document that platelet release occurs physiologically in the lungs of mice from extrapulmonary megakaryocytes and that this release accounts for ∼50% of total platelet production.