During 7 days of incubation in vitro the trophozoite stage of the free-living soil amoeba, Acanthamoeba polyphaga, phagocytized and killed 78–97% of the cells of three strains of Cryptococus neoformans. With one strain, incubation time was increased to nine days and 99% of the yeast cells were killed. It was calculated that during 4–9 days of incubation a single trophozoite phagocytized and killed a daily average of 84 yeast cells. The lethal effect of A. polyphaga on C. neoformans may represent a biological control mechanism in nature. Some of the surviving cells of C. neoformans developed into colonies containing pseudohyphae; these pseudolhyphal forms may be a biological ‘escape hatch’.