HER‐2/neu is a tumor‐associated antigen overexpressed in a large variety of human tumors. Eight HER‐2/neu peptides displaying HLA‐A*0201 anchoring motifs were selected and tested for their binding affinity to HLA‐A*0201 and their capacity to elicit cytotoxic T lymphocyte (CTL) responses in both HLA‐A*0201 transgenic mice and in HLA‐A*0201⁺ healthy donors. Two high‐affinity (p5 and p48) and one intermediate‐affinity (p1023) peptides triggered CTL responses in both transgenic mice and humans, comparable to those observed for the well‐known HER2/neu dominant peptide p369. CTLinduced in transgenic mice lysed HLA‐A*0201⁺ RMA cells infected with recombinant HER‐2/neu but not cells infected with wild‐type vaccinia virus. Human CTL lysed HLA‐A*0201⁺ HER‐2/neu⁺ tumor cells of different origins (breast, colon, lung and renal cancer) irrespective of the expression levels of HER‐2/neu. Importantly, primed CTL specific for theseepitopes were detected in freshly isolated tumor‐infiltrating lymphocytes from three renal cell carcinoma patients. Therefore, the HER‐2/neu peptides p5, p48 and p1023 may be good candidates for immunotherapy of a broad spectrum of tumors, including renal cell carcinoma.