The human CD59 gene encodes a cell surface antigen detected by MEM43 and other antibodies. It has homology to the mouse Ly-6 genes that map on mouse chromosome 15 and are involved in lymphocyte signal transduction. CD59 may play a role in protecting against complement-mediated lysis. The human CD59 gene had been previously localized to 11p13-p14. We expected, on the basis of synteny arguments, that CD59 would map in 11p14. However, we have precisely localized the human CD59 gene to band p13 of chromosome 11 by somatic cell genetics and by pulsed-field gel electrophoresis; indeed the gene is often deleted in WAGR individuals. This region of chromosome 11 is syntenic with mouse chromosome 2. This suggests that CD59 is not a homolog of the mouse Ly-6 genes on mouse chromosome 15, but rather is a related gene. The human CD59 gene is shown to map within 500 kb of another cell surface marker, MIC11, the gene for which has not been cloned. This localization and the results of immunoprecipitation experiments suggest that the CD59 gene could encode the MIC11 antigen; alternatively this region of 11p13 may contain a cluster of genes encoding cell surface molecules.