In biopsy specimens of B-cell chronic lymphocytic leukemia, large cells with cytologic features of Reed-Sternberg cells and mononuclear Hodgkin's cells are an uncommon occurrence. The nature of these large cells has not been fully elucidated, and the relationship of these cases with Hodgkin's disease is unclear. Immunophenotypic analysis of a case of chronic lymphocytic leukemia with interspersed Reed-Sternberg cells showed that the large cells were positive for CD45 (LCA), various B-cell markers (CD19, CD20, CD22), and CD30 (Ki-1), but were negative for CD15 (Leu-M1), suggesting that they represented activated neoplastic B cells. These results were compared with those reported in the literature.