Abstract We have molecularly delineated a Drosophila β-amyloid protein precursor-like (Appl) gene and analyzed its pattern of expression. Appl defines a new locus within the IB division of the X-chromosome, a region previously shown to be important for neural development. The genomic limits of the Appl gene were defined by mapping of the Appl cDNAs. The Appl transcript spans ∼38kb (1kb=103 base-pairs) of genomic DNA. Genomic regions surrounding the first two exons were sequenced. The first exon contains 78 nucleotides of the coding sequence and is separated from the second exon by a ∼21 kb intron. The second exon is 171 nucleotides long and is separated from the third exon by a ∼7 kb intron. We present in situ RNA localization data that demonstrate that the Appl transcript is found in post-mitotic neurons in all developmental stages, in the central and peripheral nervous systems. Within the nervous system transcripts are not observed in neuroblasts, newly generated neurons and at least one class of presumed glial cells. The temporal and spatial specificity of Appl expression suggests that the gene product has a function that is common to most neurons. Appl cDNA predicts an 886-amino acid polypeptide that exhibits strong sequence similarity to the human β-amyloid protein precursor (APP) (Rosen et al. 1989). In this paper, we compare the Appl gene expression with the pattern of expression of the β-amyloid protein precursor (APP) gene in mammals. Furthermore, we suggest that during evolution, a neural-specific function encoded by the APP gene has been selectively maintained.