We report the characterization of a chromosomal integrin gene that encodes the Drosophila PS2 alpha subunit. The gene is composed of 12 exons spanning 31 kb. By employing a novel method for directed cDNA cloning, we have analyzed over 300 independent cDNA clones for the existence of alternate RNA products. Two forms of PS2 alpha mRNA are frequently observed: a canonical (C) form and a form lacking the 75 nucleotide exon 8 (m8). The relative ratio of these two forms varies widely during development. Although region A, derived from exon 8 and the adjacent 25 amino acids, shows weak conservation among the sequences of alpha subunits that bind to different ligands, it is highly conserved in the homologous PS2 alpha gene of the distantly related Mediterranean fruitfly. We suggest that the variable region A may be important in determining the specificity and affinity of integrin receptors for their ligands.