The c-fgr proto-oncogene is a member of the src family of intracellular protein tyrosine kinases. C-fgr is selectively expressed in hematopoietic cells, particularly in monocytes, neutrophils and natural killer cells. Although c-fgr is presumed to play a role in signal transduction, its normal function has not been completely elucidated. In contrast to all other members of the src family, the presumed murine and human c-fgr homologues have a low degree of homology in their amino terminal domains which likely mediate the association of c-fgr proteins with signalling complexes and other targets; murine and human c-fgr proteins exhibit other functional differences as well. In contrast to human C-FGR, the murine C-FGR genomic locus has not been characterized. We have now isolated and mapped three overlapping phage clones spanning 33 kb of the murine C-FGR genomic locus. Contained within these clones are 18 kb of DNA containing the C-FGR coding exons (exons II-XII), one 5' untranslated region exon (exon Ib) located 1.7 kb upstream of exon II, 6.5 kb of DNA upstream of exon Ib and 6.7 kb of DNA downstream of the polyadenylation site in exon XII. From exons Ib-XII, the exon-intron organization, exon-intron junctions and intron lengths of the murine and human C-FGR genomic loci are quite similar; with the exception of exon II, the exon lengths are also quite similar. Although these studies suggest that the murine and human C-FGR genes are in fact homologues, the organization of these genes upstream of exon Ib is quite divergent.