Expression of cytochrome b558, an essential constituent of the superoxide generating system in phagocytes, was demonstrated in B-lymphocytes. To determine its expression in malignant lymphoma (ML), 103 non-Hodgkin's MLs and 18 Hodgkin's (HD) MLs, together with non-tumorous lymphoid tissues were immunohistochemically analyzed, using two antibodies specific for the cytochrome. In non-tumorous tonsils and lymph nodes, B-lymphocytes, especially in the mantle zones, and histiocytes stained heavily, while T-lymphocytes failed to stain. Among the 55 B-MLs, all follicular lymphomas (9/9) and 18/46 of the diffuse lymphomas were found to express cytochrome b558. Among 48 T-MLs, 46 were unstained by antibodies against the cytochrome. The two cytochrome b558-positive cases were CD 30-positive anaplastic large cell lymphomas. Sixteen of 18 HD patients had CD 30-positive Reed-Sternberg cells which also stained with antibody alpha LC (an anticytochrome b558 antibody). Thus, cytochrome b558, represents a new lymphocyte differentiation antigen.