Lysis of ectromelia- or LCM virus-infected macrophage target cells by virus-specific cytotoxic T cells from mice immunized with the homologous virus occurred only where donors of T cells and target cells shared eitherH-2KorH-2Dgenes. With both viruses, use of T cell or target cell donors bearing mutations (B6.C-H-2ba, B6-H-2bh, B6-H-2bg1, and B6-H-2bg2), all of which apparently occurred in the same single genetic element in theH-2Kbregion, abolished (H-2ba) or impaired (H-2bh,H-2bg1andH-2bg2) lysis in T cell-target cell combinations that shared (apart from the mutations) all other genes in theK, I-A, orI-Bregions of theH-2complex. The data suggest that virus-induced antigenic patterns on infected B6.C-H-2ba(mutant) cells are more different antigenically from those on C57BL/6 (wild type) cells than are those on infected cells from the other mutants -B6-H-2bh, B6-H-2bg1, and B6-H-2bg2. (B6.C-H-2ba× B6 -H-2bh)F1mice behaved like B6-H-2bh, indicating no complementation, and confirming that theH-2Kgene(s) involved in recognition of virus-infected cells by virus-specific T cells behave as a single element. These findings are discussed in relation to the nature of virus-induced antigenic patterns that are recognized by virus-specific cytotoxic T cells.