It is now clear that NK cells can perform 'missing self' recognition, that is eliminate cells because these fail to express certain critical MHC class I products adequately. Although isolated NK cell subsets can be turned off by self as well as non-self MHC molecules, genetic studies, mainly in vivo, argue that NK cells always learn to spare cells expressing critical self MHC alleles. This article reviews work on receptor expression and specificity of NK cells in MHC class I transgenic mice. A 'receptor calibration' model is proposed to account for how NK cells can interact with self as well as non-self MHC and adapt their receptors to perform optimally to detect alterations of self MHC.