We describe the molecular characterization of the Drosophila gene crumbs, which encodes an integral membrane protein with 30 EGF-like repeats in the extracellular part and exhibits a striking expression pattern. The protein is exclusively localized on the apical membranes of epithelial cells and concentrated at the borders between cells. Mutations in crumbs lead to severe disruptions in the organization of ectodermally derived epithelia and in some cases to cell death in these tissues. The structure and the expression pattern of the protein and the phenotype of mutations indicate a function of crumbs during the development of epithelia, possibly for the establishment and/or maintenance of cell polarity.