The initial development of the Drosophila embryo is characterized by rapid nuclear mitosis without cytokinesis. After 13 such mitoses, a coordinated cell division process called cellularization occurs, during which membranes simultaneously enclose each nucleus in a cell. Cellularization requires the establishment of a hexagonal network of actin and myosin filaments in the cortex of the embryo; the filaments are located on the cytoplasmic face of the invaginating membrane furrows. Zygotic expression of the nullo gene is essential for the maintenance of an intact actin-myosin network. We have cloned the nullo gene and present its sequence as well as a characterization of nullo transcript levels in wild-type and mutant embryos. The nullo gene encodes a predicted protein of 213 amino acids, a large proportion of which is basic, hullo transcripts are first detectable at nuclear cell cycle 11, peak in accumulation at the end of cycle 13, and disappear rapidly as cellularization begins. The gene does not appear to be expressed at any other time in the life of the organism. The normal accumulation of nullo transcripts does not require gene activity of other zygotic cellularization genes. The regulation of hullo RNA levels during cycle 14, however, is coupled to the nucleocytoplasmic ratio, which also controls the cessation of rapid, synchronous mitosis just before cellularization.