We have studied two anti-p185 antibodies: the monoclonal antibody 7.16.4 and rhuMAb 4D5, which were raised against the the ectodomain of rat (p185neu), and the human (p185her2/neu) homolog, respectively. Studies on the structure of these two antibodies indicate that they share structural similarity in the variable region, especially the CDR3 region, which determines the antibody–antigen interaction. Further studies by flow cytometry revealed that 7.16.4 can compete with rhuMAb4D5 for binding to the cell surface p185her2/neu, suggesting that these two antibodies share an epitope on the p185 receptor. Furthermore, 7.16.4 can also inhibit proliferation and transformation caused by p185her2/neu. Moreover the rhuMAb 4D5 binds to the rat p185neu. With the observation that 7.16.4 positively stains human breast cancer tissues that overexpress p185her2/neu, 7.16.4 may be useful for the pathological diagnosis and therapy of human tumors.