We have constructed a physical map of a >2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode >17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show thatNkrp1genes are clustered in a region flanked byA2mandCd69genes and that mostLy49genes are clustered in a distal region ∼1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes,Cmv1andRmp1.The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.