We have developed a monoclonal antibody that detects the first human B-cell-specific differentiation antigen expressed on transformed B lymphoblasts. The antigen is termed B-LAST 1 and is found on B cells transformed in vitro with Epstein-Barr virus (EBV) and pokeweed mitogen; in vivo with EBV and antigen; and on neoplastic B cells from chronic lymphocytic leukemia and poorly differentiated lymphoma. The antigen has a molecular weight of 45,000 and was not found on cells of T, null or myeloid lineage, whether obtained from peripheral blood, lymph nodes, neoplasms or cell lines. The antigen is expressed at a much higher level on EBV-infected cells than on any other cell type studied, but does not appear to be virally encoded. The significance of this antigen in the process of viral and nonviral transformation and its possible role as a target for T-cell-mediated immunity against virus-infected cells is discussed.