Cytotoxic T cells taken from an individual recovering from a viral infection are capable of killing only virally infected cells which share an MHC haplotype with the host (MHC restriction). Very recently extensive allelic polymorphism of MHC class I genes has been demonstrated in both elasmobranchs and teleosts. Accordingly, we should use effector and target cells with the same MHC haplotype to study the MHC-restricted, antigen-specific cytotoxic T cell response in fish. In this symposium our recent studies on polymorphism and function of shark and rainbow trout MHC I genes were first described, followed by MHC-restricted cell-mediated cytotoxicity against virus-infected cell lines using homozygous clonal rainbow trout (C 25 clone) sensitized by DNA immunization with IHNV-G or by infection with IHNV and trout cell line (RTG-2) which shares the same MHC I allele with the trout.