To determine if activation-induced cytokine production is altered in CD2+ lymphocytes from B-CLL patients, cytokine levels were determined by ELISA in supernatants of PHAstimulated cultures of CD2+ cells from 33 B-CLL patients and 22 healthy controls. The production of Interferon ␥ (IFN-␥) and Tumor Necrosis Factor (TNF-␣) by mitogenactivated CD2+ lymphocytes from B-CLL patients was higher than that found in healthy controls, while no differences were found in TNF- production. IFN-␥ and TNF-␣ levels determined at 72 h in PHA-stimulated CD2+ cell cultures from B-CLL patients statistically correlated with the percentages of CD3+CD45RO+ and CD3-CD56+ lymphocytes, respectively. Although there were differences in the production kinetics of interleukins (ILs) 2 and 4 between B-CLL patients and the healthy controls, no differences were found at the time when the levels of both interleukins peak. The production of both IFN-␥ and IL-4 by PHA-stimulated CD2+ lymphocytes from non-smouldering B-CLL patients was significantly higher than that from smouldering B-CLL patients while no significant differences were found in the production of IL-2, TNF-␣, and TNF- between the two B-CLL patient groups. These data suggest that functional alterations in the production of cytokines by CD2+ cells from B-CLL patients could help to explain the expansion of leukemic cells in B-CLL patients. Am.