In order to establish human monoclonal antibodies to any sort of antigens efficiently, we have made following two approaches. Our first approach is to improve cell fusion frequency. By improving our previous method for production of human hybridomas, we obtained higher frequency (1/700 vs. 1/5500) compared with our previous method by adding irradiated myeloma cells to culture of fusion cells and modifying the selective medium. Our second approach is to use a SCID-hu mouse for immunization. Since the injection of human PBL can result in the stable long-term reconstitution of a human immune system in SCID mouse, we tried to immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse, we obtained human IgG antibodies to KLH. Additionally, we succeeded in establishing human B lymphoblastoid cell lines which produced antibodies specific to KLH. These methods will open new prospects for the detection and therapy of cancer.