We have examined the immunoglobulin gene configurations in cell lines from eight patients with diffuse histiocytic lymphoma in order to establish the cellular lineage and stage of differentiation of these lymphomas. The presence of heavy and light chain gene rearrangements as well as heavy chain class switching in seven cells placed these tumors within the B cell lineage. In contrast, one cell (SU-DHL-1), which lacks B cell-restricted surface antigens, retained germline heavy and light chain loci, indicating that it may represent a true histiocyte or uncommitted cell. Truncated RNAs for both the heavy and light chain immunoglobulins were responsible for the lack of surface immunoglobulin in the SU-DHL-2 cell line. Another cell line (SU-DHL-6), which possesses a t(14;18)(q32;q21) translocation, demonstrated an unexpected recombination within its heavy chain gene locus that may be the interchromosomal breakpoint.