Previous work has demonstrated expression of the larval serum protein-2 gene, Lsp-2, uniquely during the late larval and pupal stages of development in Drosophila melanogaster. Here we report that the LSP-2 polypeptide accumulates in the hemolymph throughout adult life as well. Western blot analysis using an LSP-2 antiserum reveals notable differences in the molecular weight of the larval and adult polypeptides. Lsp-2 transcription results in a unique mRNA of 2.3 kb, exhibiting the same 5′ end in both larvae and adults. However, adult Lsp-2 mRNA is only expressed at 1% of the high level detectable in late third-instar larvae. Whereas Lsp-2 mRNA accumulates uniformly in all fat body cells of third-instar larvae, over 80% of the adult Lsp-2 transcript is expressed in the adipose tissue of the head. These results suggest a differential regulation for expression of the Drosophila Lsp-2 gene in adults and larvae.