The participation of hamster T cells in a variety of putative MHC-determined reactions was studied utilizing a well-characterized, highly selective goat anti-hamster thymocyte (G alpha HT) serum. Hamster lymphoid cell suspensions treated with G alpha HT lose much of their capacity to induce local graft-versus-host reactions and to function as responder cells in mixed lymphocyte reactions. In contrast to the participation of hamster T cells in alloimmune reactions (MLR and GVHR), virus-induced, cytotoxic activity in hamsters undergoing acute virus infection is not T-cell-mediated. This latter finding was rather surprising in view of the major role played by cytotoxic T effector cells in comparably infected mice and rats. These results suggest that, although hamsters are able to respond to putative class II MHC disparities in allogeneic reactions, MHC-encoded molecules, presumably class I, are not utilized for induction of effective cytotoxic activity in response to acute virus infection in this species. The implications of these findings are discussed in relation to our present understanding of the hamster MHC.