Peripheral blood from 121 consecutive adult patients with B-cell chronic lymphocytic leukemia (B-CLL) was immunophenotyped, and three groups with differing surface immunoglobulin (sIg) expression patterns were identified: Group A, 82 patients (68%) with weak sIg expression in greater than 20% of the circulating lymphocytes; Group B, 16 patients (13%) with either undetectable sIg or weak sIg expression limited to less than 20% of the lymphocytes; and Group C, 23 patients (19%) with strong sIg expression in greater than 20% of the lymphocytes. The histories of these patients were reviewed retrospectively, and the median follow-up in Groups A, B, and C was nine, ten, and nine years, respectively. Disease progression, defined as the development of cytopenia(s) (hemoglobin less than or equal to 100 g/L [less than or equal to 10 g/dL] or platelet count less than 100 X 10(9)/L [less than 100 X 10(3) microL]) and/or the development of newly palpable splenomegaly or lymphadenopathy, was least in Group B (6%) versus Group A (34%) versus Group C (30%) (P = 0.08). The incidence of hypogammaglobulinemia among patients who had protein electrophoresis performed was 7% in Group B versus 46% in Group A versus 45% in Group C (P = 0.036). The authors conclude that adult patients with B-CLL in whom sIg is undetectable or weakly expressed in less than 20% of the circulating lymphocytes may have an even more indolent clinical course than those with more widespread sIg expression.