We describe the effects of mutations in the fizzy gene of Drosophila melanogaster and show that fizzy mutations cause cells in mitosis to arrest at metaphase. We show that maternally supplied fizzy activity is required for normal nuclear division in the preblastoderm embryo and, during later embryogenesis, that zygotic fizzy activity is required for the development of the ventrally derived epidermis and the central and peripheral nervous systems. In fizzy embryos, dividing cells in these tissues arrest at metaphase, fail to differentiate and ultimately die. In the ventral epidermis, if cells are prevented from entering mitosis by using a string mutation, cell death is prevented and the ability to differentiate ventral epidermis is restored in fizzy; string double mutant embryos. These results demonstrate that fizzy is a cell cycle mutation and that the normal function of the fizzy gene is required for dividing cells to exit metaphase and complete mitosis.