The twelve sequenced Drosophila genomes show the vast majority of neurohormone and neuropeptide genes to be very well conserved. Nonetheless, the gene encoding the hormone neuroparsin has undergone significant evolution. Although Drosophila melanogaster has one of the best known genomes, no neuroparsin gene can be detected in either the assembled genome or any of the individual sequencing traces. This gene is similarly absent from the genomes of other species in the melanogaster subgroup, even though it is present in the genomes of eight other Drosophila species. Transgenes in which the promotor of the Drosophila ananassae neuroparsin gene drives expression of gal4 show no expression in D. melanogaster. The hypothesis that this gene has been lost from the melanogaster subgroup is also supported by the neuroparsin gene of Drosophila auraria. In this species, of which the genome has not been sequenced, but which stands phylogenetically between D. ananassae and D. melanogaster, the predicted neuroparsin has lost half its normal size, including four of the twelve conserved cysteine residues. These findings demonstrate that a hormone which plays important regulatory roles in development and reproduction in hemimetabola and is important in mosquito reproduction, has lost its relevance in the melanogaster subgroup of the genus Drosophila. If the essential role of neuroparsin in larval hemimetabola is to ensure the gradual progression from a larval into an adult form during development, that role might become superfluous in some holometabola. In mosquitoes the role of neuroparsin in reproduction appears similar to that of the insulin-related hormones. Perhaps the combination of the development of a complete metamorphosis and a redundant role in reproduction made neuroparsin dispensable in some Drosophila species.