Nine different CTL epitopes, conserved in both Hantaan virus (HTNV) and Sin Nombre virus (SNV), were selected for study. The binding affinity of each peptide with HLA-A2.1 molecules in vitro was determined and antigen-specific responses from seven donors who had a previous field infection with HTNV were examined. Although the strength or frequency of CTL activity showed different patterns in the seven patients, five of seven patients showed significant activity against at least one or more epitope peptides. In particular, the peptide ILQDMRNTI (HTNV, aa 334-342; SNV, aa 333-341), which elicited CTL activity in five patients, was shown to be specifically HLA-A2.1-restricted in partially cloned CD8+ T cells and also induced activated and effector CD8+ T cell-producing T cytotoxic (Tc) type 1 cytokines, such as IL-2 and IFN-gamma. The results suggest that this epitope would serve as a useful component for the intervention of both HTNV and SNV infection.