The purpose of the present invention is to provide a method for selectively and efficiently preparing antigen-specific monoclonal antibody-producing hybridomas, and a method for efficiently producing antigen-specific monoclonal antibodies. The present invention provides a method for producing antigen-specific antibody-producing hybridomas, the method including: a non-human animal immunization step in which antigens are administered to immunize a non-immunocompromised non-human animal； a transplant step in which secondary lymphoid tissue or secondary lymphoid tissue cells are collected from the non-human animal immunized in the immunization step, and the secondary lymphoid tissue or the secondary lymphoid tissue cells is/are transplanted to an immunodeficient non-human animal； an immunodeficient non-human animal immunization step in which the antigens are administered to immunize the immunodeficient non-human animal that underwent transplantation in the transplantation step； an acquisition step in which splenocytes or lymph node cells are acquired from the immunodeficient non-human animal immunized in the immunodeficient non-human animal immunization step； and a hybridoma preparation step in which antibody-producing hybridomas are prepared by fusing the splenocytes or the lymph node cells acquired in the acquisition step with myeloma cells.
