We established an anti‐ErbB‐2 mouse‐human chimeric monoclonal antibody (MoAb), CH401, which was able to kill cancer cells overexpressing the ErbB‐2 protein in vitro. The analysis of the killing mechanism indicated that MoAb CH401 might be the first anti‐ErbB‐2 mouse‐human chimeric MoAb which can induce the apoptosis of cancer cells, since morphological changes and DNA fragmentation were recognized in MoAb CH401‐treated cells. The ErbB‐2 receptor appears to have two opposing functions: acting as a receptor both for a growth factor and for an apoptotic factor. Our results indicate that MoAb CH401 treatment may prove to be very useful for cancer therapy.