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We studied the effects of B cell directed growth factors on B lymphocytes from 11 patients with chronic lymphocytic leukemia (B-CLL). B-CLL lymphocytes were costimulated with anti-mu antibody (Ab) and with three growth factor preparations: recombinant IL2, B cell growth factor (BCGF) (20 kiloDalton (kD) BCGF) and a high molecular weight BCGF (50 kD BCGF). IL2 was the more active factor (in six of 11 patients). The effect of IL2 was dependent on a costimulation with anti-mu Ab or occurred independently of anti-mu Ab, according to the patients. This pattern of reactivity did not correlate with the presence or absence of the IL2 receptor (IL2-R) molecule on fresh B-CLL lymphocytes. Five patients responded to the 20 kD BCGF. Although four of them were also strong responders to IL2, one strongly responded to the 20 kD BCGF and did not respond to IL2. Only one patient responded to the 50 kD BCGF. When an anti-IL2-R Ab was introduced into the culture, only the responsiveness to IL2 was abolished: thus both 20 kD and 50 kD BCGFs activate B-CLL lymphocytes independently of the IL2-R. These results show that several B cell directed growth factors can act independently to support the proliferation of B-CLL lymphocytes.