CD19 is a B lymphocyte cell-surface marker that is expressed early during pre-B-cell differentiation with expression persisting until terminal differentiation into plasma cells. CD19 is a member of the Ig gene superfamily with two extracellular Ig-like domains separated by a non-Ig-like domain, and with an extensive approximately 240 amino acid cytoplasmic domain. In this study, Southern blot analysis revealed that the human and mouse CD19 genes were compact single copy genes. Both the human and mouse CD19 genes were isolated and the nucleotide sequences flanking each exon were determined. Both genes were composed of 15 exons and spanned approximately 8 kilobases (kb) of DNA in human and approximately 6 kb in mouse. The positions of exon-intron boundaries were identical between human and mouse and correlated with the putative functional domains of the CD19 protein. The 200 bp region 5' of the putative translation initiation AUG codon was well conserved in sequence between human and mouse and contained potential transcription regulatory elements. In addition, the 3' untranslated regions (UT) of the CD19 genes following the termination codon were conserved in sequence. The high level of conservation of nucleotide sequences between species in all exons and 5' and 3' UT suggests that expression of the CD19 gene may be regulated in a similar fashion in human and mouse.