Cellularization of the Drosophila embryo requires the establishment of a hexagonal network of actin and myosin filaments that are interconnected around the nuclei in the cortex of the syncytial blastoderm. This cytoskeletal network provides the framework and possibly the contractile force for the membrane invaginations that synchronously subdivide the syncytial embryo into individual cells. Zygotic expression of the nullo locus is essential for the preservation of an intact actin-myosin network. Embryos deleted for the nullo locus have a disrupted network, resulting in the formation of many multinucleate cells. We show that nullo is not required for the initial formation of the actin-myosin network, but is necessary for the maintenance of its hexagonal shape during cellularization. The phenotype of embryonic mosaics is nonautonomous, indicating that nullo does not have to be expressed in every nucleus for proper cellularization. Examination of nullo mutant clones in adults reveals that nullo activity is not required for cell division in imaginal discs. Furthermore, germline clone experiments suggest that maternal expression of the nullo locus is not essential for either germline proliferation or the cellularization of progeny. We propose a model in which nullo functions specifically at cellularization to stabilize the actin-myosin network during contraction.