We have mapped the PLCG2 gene, which encodes the enzyme phosphatidyl inositol-specific phospholipase C-gamma 2. This is one of the phospholipases responsible for catalyzing the hydrolysis of phosphatidyl inositol in response to a great many mitogenic stimuli. PL C-gamma 2 is an essential component of the signal transduction pathway between tyrosine kinases and downstream events such as protein kinase C activation and intracellular calcium release. We assigned PLCG2 to human chromosome 16 by amplification within a somatic cell hybrid mapping panel. To position the locus at a much finer resolution, PLCG2 sequences were amplified from a chromosome 16-specific somatic cell hybrid panel, which placed the gene on the long arm of the chromosome in band 16q24.1, a region that has few known genes. We have hybridized a mouse Plcg2 open reading frame probe to mouse DNAs from the European Interspecific Backcross. The segregation pattern reveals the mouse Plcg2 locus maps to distal chromosome 8.