The combined phenotypic expression of CD11c(low)B220(+)CD122(+)DX5(+) has been used to define a novel cell type termed IFN-producing killer dendritic cells (IKDC). IKDC readily produce IFN-gamma and demonstrate spontaneous cytotoxic activity toward tumors, suggesting that a modulation of IKDC number may be beneficial in cancer treatment. We examined various mouse strains and found that IKDC number was highly variable between the different strains. A linkage analysis associated the distal arm of chromosome 7 with variations in IKDC number. The genetic contribution of chromosome 7 to the regulation of IKDC number was confirmed through the use of congenic mice. We further demonstrate that IKDC proportion is regulated by intrinsic hematopoietic factors. We discuss the role of various candidate genes in the regulation of this newly described cell type and its implication in therapy.