HLA class I antigens of the human major histocompatibility complex (MHC) play an important role in immune response. Consistent with their role in immune surveillance, these antigens are expressed on most cell types. However, a marked deficiency or lack of expression of these antigens has been observed in a variety of human neoplasms. We have shown that a number of class I-deficient human tumor cell lines, including small-cell lung carcinoma, lacked products of MHC-encoded TAP1 and LMP2 genes. Since a direct evidence for the role of these genes in class I expression in tumor cells is not available, in the present study we transfected class I-deficient human small-cell lung carcinoma cells with cDNAs corresponding to TAP1 gene and to LMP2 gene. Following transfection, tumor cells expressed products of the respective transfected gene. Cell-surface expression of class I molecules was, however, observed in cells transfected with TAP1, but not in tumor cells transfected with LMP2 gene. Our results provide conclusive evidence for a role of TAP1 gene in class I expression and suggest that transfection of TAP genes may be useful to upregulate class I expression in tumor cells. This strategy for restoration of class I expression by transfection of TAP genes is relevant for tumor rejection and/or abrogation of metastases formation.