Normal lung defense starts with the mucociliary escalator and alveolar macrophages that engulf and destroy inhaled particles. When *Histoplasma* spores reach the alveoli, macrophages phagocytose them as they would any invader. Here is the twist that defines the pathogen: instead of being killed, the fungus survives and replicates inside the macrophage as a yeast. It becomes an intracellular organism, which is exactly why treatment relies on antifungal drugs rather than on the host simply outmuscling it, and why tissue samples show yeast packed inside macrophages. Over the following one to two weeks, before adaptive immunity matures, the yeast-laden macrophages travel through lymphatics and the bloodstream, so a brief, usually silent, spread through the body happens in nearly everyone infected. In a person with intact cell-mediated immunity, T lymphocytes then activate macrophages, granulomas form and wall off the organism, and the infection is contained. The healed granulomas often calcify, which is why old, symptomless histoplasmosis frequently shows up later as calcified lung nodules or calcified hilar and spleen lesions on imaging. When cell-mediated immunity is weak or absent, granulomas do not...