Zona pellucida (ZP) domain proteins have been identified in various species from worms to humans. Most of the characterized ZP family members are secreted or remain anchored to the plasma membrane where they play a structural role and/or act as receptors. In humans, several ZP proteins attracted attention because of their abundant expression in certain organs and their relation to various diseases. Here, we compare the molecular architecture and embryonic expression pattern of the 18 genes encoding ZP proteins in Drosophila melanogaster. Only five of these genes have been genetically characterized. All ZP genes are expressed in the embryo in epithelial tissues, such as the foregut, the hindgut, the Malpighian tubules, the salivary glands, the tracheal system, sensory organs and epidermis. Five genes are expressed during oogenesis; two of them are transcribed in the follicular epithelium, but not in the germ line cells.