We describe protein sequences for a uromodulin-like larval glycoprotein (LGP) from 21 species of galaxiid fishes, with a MRCA about 30 Ma. These have been derived from both genomic DNA and cDNA, by conventional and Roche 454 sequencing.LGP shows a fast rate of evolution and an exceptionally strong signal of positive selection over the entire coding region, as evidenced byAcross all sequences, 182/336 (54 %) of residues are variable; many substitutions are profound/nonconservative and include in-frame indels. Genetic distances are, on average, 2.4x larger for coding region (996 bp) than introns (1459 bp).Our initial in situ work shows that the gene is active in developing skin and gill arches, which are likely conduits for pathogens. As ZP-domain proteins have been recently categorized as members of the immunoglobulin superfamily, we believe it is likely that LGP is an immune protein, and that these fishes are engaged in a Red Queen arms race.