CD19 is a B lymphocyte cell surface protein expressed from the earliest stages of B lymphocyte development until their terminal differentiation into plasma cells. In this report the human CD19 gene (hCD19) was localized to band p11.2 on the proximal short arm of chromosome 16 by in situ hybridization to metaphase chromosomes, using hCD19 cDNA as probe, hCD19 gene localization was confirmed by polymerase chain reaction based analysis with hCD19specific primers, using a panel of human/hamster somatic cell hybrid DNA as templates. The mouse CD19 gene (mCd19) was mapped to bands F3-F4 of chromosome 7 by in situ hybridization to metaphase chromosomes, using a mCD 19 cDNA probe. Segregation analysis of nucleotide sequence polymorphisms in interspecific backcross progeny revealed linkage of mCd19 with hemoglobin [3 (Hbb), Int-2, and H19, other loci previously mapped to the same region of mouse chromosome 7, confirming the localization of mCdl9 to this region. The order of these loci was determined to be centromere -Hbb -mCdl9 -H19 -Int-2telomere. The genetic distances between the loci examined, calculated from the recombination frequencies, suggested that mCdl9 was located centrally between Hbb and H19. This region of mouse chromosome 7 is homologous to the region of human chromosome 16 to which the hCD19 gene maps. Multiple genes with a lymphocyte-related function also map to this conserved region including genes encoding the IL-4 receptor, CD1 la, CD1 lb, CD11c, CD43 (leukosialin), and protein kinase C ~ polypeptide.