OBJECTIVE To review the recent advances in the biologic and clinical research of chronic lymphocytic leukemia. METHODS English-language literature search using MEDLINE (1980 to 1990) and CANCERLIT (1980 to 1990), review of meeting abstracts and reports, and an extensive manual search of bibliographies of identified articles. METHODS Approximately 800 articles, abstracts, and book chapters were selected for analysis. METHODS The literature was reviewed and 227 articles were selected as representative of the important advances in chronic lymphocytic leukemia. RESULTS Chronic lymphocytic leukemia is a disease of lymphocytes that appear to be mature but are biologically immature. These B lymphocytes arise from a subset of CD5-B cells that appear to have a role in autoimmunity. The pathogenesis of chronic lymphocytic leukemia is likely a multistep process, initially involving a polyclonal expansion of CD5-B cells followed by transformation of a single cell. Chromosome studies indicate that trisomy 12 is the most common abnormality, followed by 14q+, 13q, and 11q. These abnormalities portend a poor prognosis. Recent progress in the treatment of chronic lymphocytic leukemia involves three new drugs: fludarabine, pentostatin, and 2-chlorodeoxyadenosine. Recent preliminary results of allogeneic bone marrow transplantation present insights into the potential curability of chronic lymphocytic leukemia. Therapy with intravenous immunoglobulin can prevent or delay moderate bacterial infections in persons with chronic lymphocytic leukemia. CONCLUSIONS Major advances in the biologic research of chronic lymphocytic leukemia have resulted in new understanding of this complex disease. New therapies, such as those with intravenous immunoglobulin and fludarabine, may lead to improved outcome.