Light and electron microscopy were used to analyze in vitro the interaction of Fonsecaea pedrosoi with in vivo activated-macrophages. Adherence of the fungi to the surface of activated macrophages triggers the respiratory burst as revealed by reduction of nitroblue tetrazolium. Transmission electron microscopy revealed NAD(PO)H-oxidase activity in the portions of the macrophage plasma of membrane that were in contact with the fungus as well as within phagocytic vacuoles. Activated macrophages failed to kill ingested fungi, but they showed a fungistatic activity delaying germ tube and hyphae formation.