Frozen sections of 30 diffuse large-cell ("histiocytic") lymphomas that had arisen in both nodal and extranodal sites were stained with immunoglobulin light-chain and heavy-chain reagents, with nonoclonal antibodies to THAT HAD ARISEN IN BOTH NODAL AND EXTRANODAL SITES WERE STAINED WITH IMMUNOGLOBULIN LIGHT-CHAIN AND HEAVY-CHAIN REAGENTS, WITH MONOCLONAL ANTIBODIES TO T and B-cell antigens, and with an esterase marker for macrophages. Fourteen lymphomas expressed immunoglobulin light chains and were shown to be monoclonal; F(ab')2 fragments were sometimes necessary to demonstrate their monoclonal nature. Mu (IgM) was the most frequently expressed heavy chain, but in many patients other heavy chains were found. None of the lymphomas stained with T-cell antibodies or the esterase; 15 did not stain for immunoglobulin, but 13 of these 15 did express Ia antigen. These immunologic markers identified eight different phenotypes. Retrospective clinical analysis of the patients suggested that those who were immunoglobulin-positive had more advanced disease and shorter survival, but confirmation of the clinical relevance of immunologic phenotype will require prospective studies.