By virtue of sequence similarity, the genes encoding CD2, CD48, CD58, and Ly-9 have been assigned to a distinct subset within the immunoglobulin superfamily. Previous gene mapping studies in human and mouse have suggested that CD2, CD48, and CD58 arose by gene duplication. Here we show the gene encoding Ly-9 to be located adjacent to CD48 and the Na,K-ATPase alpha 2 subunit gene on human and mouse chromosome 1. The proximity in human and mouse genomes of the genes encoding CD2, CD58, and the Na,K-ATPase alpha 1 subunit, and of the Ly-9, CD48, and the Na,K-ATPase alpha 2 subunit genes may be explained by the occurrence of two, successive duplication events during vertebrate evolution, and suggest that Ly-9 may also participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction.