Malignant conversion and subsequent in vivo selection can give rise to the cell populations that show stable expression of an immune escape phenotype, MHC class I deficient neoplasms. Deficiencies associated with the MHC class I down-regulation are either irreversible, such as beta2 microglobulin and class I heavy chain gene disabling mutations, or reversible. The reversible MHC class I deficiencies involve all levels of the MHC class I-restricted antigen presentation machinery. They can be repaired, at least partially and in vitro, by cytokines (IFNgamma, TNFalpha) or by DNA demethylation/histone hyperacetylation procedures. The reduced levels of MHC class I antigens result in decreased sensitivity to MHC class I-restricted, cytotoxic T lymphocyte-mediated lysis, the major component of the tumour rejection reaction. MHC class I down-regulation helps tumour cells evade the classical T cell-dependent immune responses but simultaneously imposes another, the NK cell-mediated, surveillance stimulated by the 'missing self' signals. The innate and adaptive antitumour immunity may be under some conditions interconnected: primary activation of the MHC class I-unrestricted surveillance mechanisms may lead to the production of IFNgamma by the activated NK/gammadelta T cells; the in situ produced IFNgamma may then up-regulate the MHC class I molecule expression on the tumour cell surface and in this way it may stimulate the more efficient, MHC class I-restricted, adaptive immunity. If we accept that the MHC class I down-regulation can, under some conditions, indeed be a mechanism of the tumour escape from the immune defence, the problem arises how to cope efficiently with this escape. Either therapeutic procedures aiming at up-regulation of MHC class I expression, or enhancement of MHC class I-unrestricted (CD4+, NK, NKT, gammadelta T) tumour defence effector mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL-12, IFNgamma, GM-CSF), or by the cytokine gene-based, genetically modified tumour vaccines should be considered.