We have mapped GRB2, a signal transduction gene whose protein product is an essential component of the pathway between tyrosine kinases (such as the epidermal growth factor receptor) and downstream proteins (such as Ras and Sos). We assigned GRB2 to human chromosome 17 by hybridization to a somatic cell hybrid mapping panel. To position the locus at a much finer resolution, we have isolated the human GRB2 gene in three different cosmids, which we have mapped by fluorescence in situ hybridization to the long arm of human chromosome 17 (17q24-q25). We have hybridized a human GRB2 open reading frame probe to mouse DNAs from the European Interspecific Backcross. The segregation patterns reveal that the mouse Grb2 locus maps distally on chromosome 11, and an additional Grb2-related locus is present on chromosome 4 of one of the parental strains, Mus spretus/CRC.