Here we show that Drosophila sechellia—a specialist on the fruit of Morinda citrifolia that recently diverged from its generalist sister-species, D. simulans—has rapidly accumulated loss-of-function alleles and reduced gene expression at genes affecting olfaction, detoxification, and metabolism. While D. sechellia increases expression of genes involved with oogenesis and fatty acid metabolism when on its host, many more genes show reduced expression in D. sechellia. For several functionally related genes, this decrease in expression is associated with loss-of-function alleles. The rapid accumulation of these alleles potentially affected D. sechellia’s initial adaptation to M. citrifolia, likely contributes to D. sechellia’s poor competitive ability off of its host, and increases ecological isolation between D. sechellia and its sister species. Our results suggest that a subset of genes reduce or lose function as a consequence of host specialization, which may explain why, in general, specialist insects tend to shift to chemically similar hosts. Moreover, if the accumulation of non- or weakly functional genes in a specialist enhances the ecological isolation between it and other species, then this process may explain why specialists are speciose. Keywords: comparative hybridization, gene expression Overall design: 2 species (simulans and sechella) by choice vs no-choice treatment for octanoic & hexanoic acid blend