The production of human monoclonal antibodies has been impeded by the lack of human myeloma cell lines which grow easily, fuse efficiently, clone readily, and continuously secrete large amounts of antibody. A cell line, HM 2.0, was constructed by fusing a HAT-sensitive, nonsecreting, human myeloma cell line, LSM 1.2, with cells from a patient with plasma cell leukemia. In marked contrast to LSM 1.2, which could not support the secretion of immunoglobulin, fusion of HM 2.0 with cells from spleen or peripheral blood routinely resulted in the secretion of antibody to pneumococcal polysaccharides and tetanus toxoid. The fusion efficiency of HM 2.0, as measured by growth of colonies, was greater than 1 per 1.2 X 10(3) peripheral blood mononuclear cells and the number of hybrids secreting specific antibody was greater than 1 per 1.1 X 10(5) mononuclear cells from immunized individuals. This is an improvement over our previously described human "myeloma analogue" LSM 2.7, derived by fusion of a HAT-sensitive, nonsecreting human myeloma cell line, LSM 1.1, with cells from a normal donor, as well as all previously described human lymphoblastoid and myeloma cell lines. These results demonstrate that somatic cell hybridization can be used to modify an existing cell line in such a manner as to yield a "new" cell line with the attributes necessary for the production of human monoclonal antibodies.