ABSTRACT To understand the role of the spectrin-based membrane skeleton in generating epithelial polarity, we characterized the distribution of membrane skeletal components in Drosophila ovarian follicle cells and in somatic clones of mutant cells that lack αspectrin. Immunolocalization data reveal that wild-type follicle cells contain two populations of spectrin heterodimers: a network of αβ heterodimers concentrated on the lateral plasma membrane and an αβH population targeted to the apical surface. Induction of somatic clones lacking αspectrin leads to follicle cell hyperplasia. Surprisingly, elimination of αspectrin from follicle cells does not appear to prevent the assembly of conventional βspectrin and ankyrin at the lateral domain of the follicle cell plasma membrane. However, the α-subunit is essential for the correct localization of βH-spectrin to the apical surface. As a consequence of disrupting the apical membrane skeleton a distinct sub population of follicle cells undergoes unregulated proliferation which leads to the loss of monolayer organization and disruption of the anterior-posterior axis of the oocyte. These results suggest that the spectrin-based membrane skeleton is required in a developmental pathway that controls follicle cell monolayer integrity and proliferation.