AN important feature of natural killer (NK) cell activity is the lysis of cells that have extinguished expression of some or all class I major histocompatibility (MHC) molecules^1-7. Accordingly, the Ly49A NK-cell antigen receptor has been shown to deliver an inhibitory signal to NK cells on encounter with D^d or D^k class I MHC on target cells⁴. Ly49A belongs to a family of eight or more highly related, tightly linked genes^2,8-10. Expression of Ly49A and Ly49C, another member of the Ly49 family with distinct MHC specificity, define subpopulations of NK cells that are only partly overlapping^10-12. The mechanisms regulating the expression of Ly49 family members are unknown. We show here that the Ly49A and Ly49C NK-cell receptors are each subject to allelic exclusion. Because Ly49 genes are not thought to undergo DNA rearrangement^13,14, allelic exclusion of Ly49 genes could involve a mechanism distinct from that used by B and T lymphocytes^15,16 and is likely to play an important role in the genesis of a putative NK-cell repertoire specific for class I molecules.