Phosphatidylinositol 3-kinases are a family of dual specificity lipid/protein kinases, The products of PI3K's, phosphatidylinositol (3,4,5) triphosphate and phosphatidylinositol(3,4) bisphosphate, act as second messengers connecting activated transmembrane receptors to signaling pathways that control gene transcription, proliferation, transformation, programmed cell death, adhesion, migration and vesicular transport. There is evidence that different isoforms of PI3K's activate specific signaling pathways and are thus responsible for integrating cellular responses. The elucidation of the genomic structure of the catalytic subunits is a necessary step for the investigation of the function of PI3K isoforms by inactivation of the gene in vivo. The structural organization of p110 alpha, beta, and gamma genes has been previously reported. Here we report the cloning, sequencing, and structural organization of the mouse p110 delta gene from a murine 129/Sv genomic library. The p110 delta gene consists of 22 exons and spans over 13 kb, Comparison of the genomic structure with that of p110 alpha, beta, and gamma demonstrates that the p110 delta gene shares its exon structure with p110 beta, the most closely related PI3K at the amino acid level.