A mucin-like glycoprotein, peritrophin-55 was isolated and purified from the peritrophic matrix of Lucilia cuprina larvae. When injected into sheep, peritrophin-55 induced an immune response that inhibited larval growth by 51-66% when larvae subsequently fed on sera from the vaccinated sheep. The protein may have potential use as an immunogen probably accompanying other antigens to protect sheep from the cutaneous myiasis caused by these larvae. Peritrophin-55 was uniformly distributed throughout the peritrophic matrix where it probably lubricates the surface of the peritrophic matrix and protects the midgut from invasion by bacteria. The protein consists of an 8-cysteine amino-terminal domain (peritrophin-B domain) and a carboxy-terminal proline and threonine-rich domain with high probability for extensive O-linked glycosylation. The gene consists of two exons separated by a small intron. Peritrophin-55 mRNA was only detected in the larval cardia and midgut and to a minor extent in the hindgut. Sequence upstream of the transcriptional start site contained a putative promoter region, sequence similar to an ecdysone response element, sequence related to the Drosophila transposon S element and a tetranucleotide repeat region. A putative Drosophila melanogaster ortholog or paralog of peritrophin-55 (CG7714) was located within a 3458 bp intron of the Cha gene (choline-O-acetyltransferase), but on the opposite strand. Comparison of the putative promoter regions of the peritrophin-55 and CG7714 genes revealed little similarity except for a small semi-conserved sequence that is suggestive of a common transcription factor-binding site possibly contributing to the highly restricted developmental and tissue-specific expression patterns of these genes.