To determine whether analysis of lymphocyte surface markers adds clinically useful information to the Lukes-Collins classification of lymphomas, tumors from 107 adults were histologically classified and studied for surface markers. Ninety-six cases were histologically classified as Lukes-Collins B-cell lymphomas; 87 showed B and one showed T surface markers, whereas eight had neither marker. Eleven lymphomas were histologically T-cell tumors; four of the 11 showed T surface markers, and seven had neither marker. Both the Lukes-Collins classification and surface markers identified patient groups with different clinical characteristics, chemotherapeutic responsiveness and survival. However, by combining surface markers and histologic features, additional important therapeutic and prognostic information was obtained. In each histologic class, patients whose lymphomas failed to express immunologically the histologically predicted marker had fewer responses to chemotherapy and shorter survivals than patients whose lymphomas expressed the predicted marker. Our data suggest that the analysis of surface markers in combination with the Lukes-Collins classification identifies many patients who respond poorly to current therapy and who thus require new therapeutic approaches.