The level of expression of the class-I major histocompatibility (MHC) antigen was determined in a series of human embryo cell lines transformed with either adenovirus 12 (Ad 12) early region I (EI) or adenovirus 5 (Ad 5) EI DNA or with combinations of Ad 12 early region IA (EIA) or Ad 2 EIA with activated N-ras DNA. MHC class-I antigen expression was greatly reduced in all Ad 12 transformants, compared to primary cells. Expression was also reduced in the Ad 5 cell lines transformed with EIA and EIB DNA, but levels were near normal in those lines with only EIA DNA present. Amounts of MHC class-I antigen on the cell surface, as determined by RIA and FACS analysis, generally reflected total cellular levels as determined by Western blotting. Expression of beta 2 microglobulin was also much reduced in those cell lines with low levels of MHC class-I antigen. The treatment of primary cells and all the transformants with human gamma-interferon resulted in increased expression of HLA on the cell surface. Infection of primary human cells with Ad 12 or with a series of Ad 12 mutants did not have any effect on the MHC class-I antigens present.