MHC class I molecules in the host affect the specificity of NK cells. Previous work has suggested that this specificity is conferred by the expression of products encoded by the Ly49 gene family. This gene family encodes receptors that upon specific recognition of MHC class I ligands mediate an inhibitory signal that prevents killing by NK cells. The pattern of expression of the Ly49 MHC class I binding inhibitory receptors on NK cells is thought to be adapted to the host to ensure the generation of a self-tolerant, yet functional, NK cell repertoire. In the present study we have examined the expression of inhibitory receptors (Ly49A, Ly49C, and Ly49G2) on NK1.1+ cells from B6 (H-2b) and D8 (B6 mice transgenic for H-2Dd) mice as well as corresponding TAP1 -/-, beta2m -/-, and TAP1/beta2m -/- mutants of these mice. We demonstrate that receptor expression on NK1.1+ cells can be specifically modulated by host MHC class I molecules in at least two different ways: alteration of numbers of cells expressing a given receptor and modulation of the levels of expression of a given receptor at the cell surface. The degree of this modulation varies significantly among the various receptors studied and may depend upon the nature of their MHC class I ligands. The results are discussed in relation to the influence of MHC class I molecules on the development of an NK cell repertoire.