The Leu-M1 antigen has been recently proposed as a valuable immunodiagnostic marker of the Reed-Sternberg cells of Hodgkin's disease and to be particularly helpful is distinguishing Hodgkin's disease from other lymphoproliferative disorders such as peripheral T-cell lymphomas. In this study, the authors examined paraffin-embedded tissue sections obtained from 38 patients with previously well-characterized T-cell neoplasms for the presence of the Leu-M1 antigen. The cases comprised a spectrum of T-cell malignancies and were divided into four broad clinicopathologic groups: lymphoblastic lymphoma/ leukemias (6), mature T-cell leukemias (3), peripheral T-cell lymphomas (11), and cutaneous T-cell lymphomas (18), which included both mycosis fungoides and nonmycosis fungoides types. The neoplastic T cells in 19 patients (50%) expressed the Leu-M1 antigen. The proportion of Leu-M1-positive cells and the immunostaining pattern varied greatly among these cases but correlated with mature, postthymic stages of T-cell differentiation and activation. Of particular significance was the observation that the more pleomorphic neoplastic T cells, including Reed-Sternberg-like cells, exhibited an intense cytoplasmic and membranous staining pattern which was often indistinguishable from the immunostaining pattern observed in Hodgkin's disease. The authors conclude that Leu-M1 is not a specific immunodiagnostic marker of Hodgkin's disease and has limited value in distinguishing Hodgkin's disease from T-cell neoplasms which stimulate Hodgkin's disease morphologically.