- Abstract In an attempt to define immunological parameters affected by the H- ras oncogene, we have used Balb/c 3T3 cells transfected with either H- ras ( 98 6 ), H- ras + v- myc ( 98 4 v ) or plasmid only ( 98 1 ). We found that while control and oncogene-transfected Balb/c 3T3 cells exhibit similar low sensitivity to lysis by natural killer (NK) cells, H- ras + v- myc -transfected cells could immunize syngeneic Balb/c mice and induce cytotoxic T cells (CTL) with broad specificity, that lysed all types of Balb/c 3T3 cells tested. Immunization of Balb/c mice with 98 4 v cells prevented homologous tumor formation and partially inhibited the formation of tumors derived from H- ras -transfected cells. 98 6 cells were not immunogenic in vivo and did not protect the animals from a challenge of 98 6 cells. The results suggested that CTLs but not NK effector cells were important for eliciting in vivo tumor rejection of H- ras + v- myc -transfected cells. In contrast, antigens eliciting the cytotoxic T-cell response, and possibly also the in vivo tumor cell rejection response, were expressed on all cell types tested but were immunogenic only on the surface of 98 4 v cells. We further determined major histocompatibility complex (MHC) class-I molecule expression on the outer cell surface and found that H-2K was down-regulated in H- ras -transfected cells. The results support the observation that oncogenes can down-regulate specific MHC antigens, thereby preventing presentation of tumor antigens and allowing tumor escape from immune recognition.