We report on the T-cell profile and natural killer (NK) function in 22 hairy cell leukemia patients before and 2 and 6 months after a single 7-day course of 2-CdA therapy at a dose of 0.1 mg/kg daily continuous infusion. Before treatment, two groups of patients were identified in respect to NK activity: the first (12/22) had a normal number of T and NK cells and a normal NK activity, the second (10/22) showed a severe reduction of CD3+, CD4+, CD16+, and CD56+ cells, together with impaired NK activity. All patients had increased serum levels of the soluble interleukin 2 receptor (sIL-2R). Along with a high complete remission rate (77%), treatment with 2-CdA produced a significant reduction (p = 0.001) of total lymphocytes (from 1.59 x 10(9)/l to 0.72 x 10(9)/l), and particularly of CD4+ cells (from 0.68 x 10(9)/l to 0.23 x 10(9)/l), while CD8+, CD16+ and CD56+ cells were less affected. Despite the dramatic reduction of lymphocytes which lasted for more than 6 months, 7/10 patients with impaired NK function before starting 2-CdA therapy normalized the cytotoxic function within 2 months. In conclusion, 2-CdA produces a severe reduction of lymphocytes in general, and of CD4 lymphocytes in particular, whilst it may produce a significant increase in the proportion of NK cells leading, together with a normalization of the sIL-2R serum levels, to a rapid restoration of the NK cytotoxic function in the majority of patients.