Using 14 well-defined (clustered) monoclonal antibodies (MAbs) against B-cell restricted/associated differentiation and activation (CD) antigens and 12 mediastinal clear-cell lymphomas (MCCL), 46 follicular-center-cell lymphomas (FCCL), and 20 non-neoplastic lymph nodes--including toxoplasmic and HIV-associated lymphadenitis--were immunohistochemically examined to determine the histogenesis of MCCL. Antigenically, MCCL was characterized as CD5-, CD10-, CD19+, CD20+, CD21-, CD22+, CD30-, CD37+, CDw40+, and by a frequent expression of CD11c and CD23, while other antigens were inconsistently expressed. The antigenic profiles of MCCL and FCCL showed statistically significant differences in 4/14 distinct antigens. When the neoplastic cells of both tumor groups were compared with morphologically defined normal B-cell types, the overall resemblance of their immunophenotypes was even closer between MCCL and sinusoidal (monocytoid) B cells than between FCCL and follicular-center B cells. We conclude that MCCL is a lymphoma type distinct from FCCL, most probably representing a highly malignant neoplasm corresponding to sinusoidal B-cell reaction.