Pleural effusion in chronic lymphocytic leukemia (CLL) is a relatively rare phenomenon. We report a case of a pleural effusion associated with B-cell CLL but with predominantly reactive T lymphocytes in the effusion. A cell surface phenotype study showed that T lymphocytes predominated in the pleural effusion, although B lymphocytes were predominant in the peripheral blood. Genotypic analysis of the cells in the peripheral blood, bone marrow, lymph node, and pleural effusion showed the same rearrangement pattern of the immunoglobulin heavy chain genes consistent with a B-lymphocytic neoplasm (CLL). A pleural biopsy demonstrated diffuse infiltration of lymphoid cells. Most of the cells demonstrated T cell markers, although some cells revealed B cell markers by immunologic staining. These results suggested that the pleural involvement by B-CLL may have caused a reactive T-lymphocyte proliferation in the pleura and pleural effusion. To our knowledge, this is the first published case indicating that genotypic analysis of immunoglobulin heavy chain gene rearrangement may be useful in the diagnosis of a pleural effusion associated with B-cell CLL.