The role of H-2- and T-region products in determining allogeneic cell rejection was evaluated in H-2 congenic and recombinant mice by transplanting A1ATH and A6ATL leukemia cell lines induced in A.TH and A.TL strains, respectively, by Moloney murine leukemia virus.--In K- or D-region incompatible hosts transplant failure was observed, while in I + T-region incompatible hosts either rejection or prolonged survival was seen. In mice preimmunized with spleen cells from I- and/or T-region incompatible donors, leukemia cells were rejected by mice immune only to T-region products, and accepted by mice immune only to I-region products.--Cell-mediated cytotoxicity studies confirmed in vivo results. Secondary CTLs specifically directed against I-region products did not lyse the A1ATH and A6ATL cells, and secondary CTLs from A.TH and A.TL mice sensitized against A6ATL and A1ATH cells respectively exerted a lytic action specific for T-region products, while no activity was observed against I determinants.--The data suggest that tumor-transplant rejection may also be governed by histocompatibility antigens encoded in the T region.