The expression and function of IL-2R chains expressed on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed. IL-2R alpha was expressed in 31 out of 34 studied cases; in 17 cases more than 50% of the cells were positive whereas in three cases the proportion of IL-2R alpha+ cells was less than 10%. In two patients, 6 and 13% of the cells were IL-2R beta+, in six other cases only 2-3% of the B-CLL cells could be stained with the TU-27 moAb whereas in all other cases no positive cells could be detected. Equilibrium binding experiments using 125I-rIL2 revealed high (seven out of 15 studied cases), intermediate (four out of 15 cases) and low (five out of 15 cases) affinity IL-2R. The number of high and intermediate affinity IL-2R was low (range: 145-800 and 40-2800 binding sites/cells, respectively). In all cases investigated, both IL-2R alpha and IL-2R beta chain mRNA could be detected, although their quantity was variable from patient to patient. Exogenous recombinant IL-2 induced, in a dose-response manner, cell proliferation in ten out of 23 cases and this effect was independent of the expression of IL-2R alpha; however, only cells expressing high affinity IL-2R could respond to exogenous rIL-2. Moreover, anti-IL-2R alpha moAb could inhibit both spontaneous (in three out of five cases) and IL-2-induced (in five out of five cases) B-CLL cell proliferation. These findings demonstrate that in a subgroup of B-CLL, leukemic cells are dependent on the IL-2/IL-2R system whereas in another group, although cells expressed functional IL-2 binding sites, they could not respond to the mitogenic signal of IL-2.