A cell--cell hybrid of a Chinese hamster ovary (CHO) cell line and human peripheral blood lymphoblasts from a patient with B-cell chronic lymphocytic leukemia produces a surface antigen detectable by a monoclonal antibody. This surface antigen can be detected at significant levels on a fraction of chronic lymphocytic leukemia cells, but not on normal human lymphocytes from peripheral blood or bone marrow. Two different clones capable of transforming mouse cells to produce the surface antigen were isolated from a gene library of the hybrid cell by identification of small portions of the library containing functional genes, followed by detection of clones with human-specific reiterated sequences. Both clones also contain CHO-specific reiterated sequences and are therefore human--CHO recombinants. From the frequency of antigen-producing clones in the library, we estimate that they were present in the hybrid cell genome at a copy number of 100 to 1000.