Prompted by observations of HSCT (Ruggeri et al., 2002), responses to viral infections (Khakoo et al., 2004), and success in pregnancy (Hiby et al., 2004), it is now appreciated that HLA-C reactive KIR play a critical role in NK cell function, but must be examined in the context of their ligands. This evidence concerns the gene HLA-C and viral infectious disease.