Interleukin 15 (IL-15) shares many functional properties with interleukin 2 (IL-2), although both cytokines probably also exert distinct functions. In order to screen for functional differences between IL-2 and IL-15 with respect to the control of T cell functions, we have stimulated human T lymphoblasts (hTBl) with IL-2 and/or IL-15 and have assessed the resulting changes in the following parameters: T cell proliferation; expression of various relevant surface markers; cytokine and receptor (alpha-chain) transcription; and IL-2 and IL-15 activity. Both cytokines equally upregulate standard activation markers such as CD25 and CD95 and downregulate CD27. However, IL-2 upregulates CD30, TNF receptor type II and CD40L expression significantly stronger than IL-15. IL-15 potentiates Con A-induced IL-2 secretion. Even though hTBl transcribe the IL-15 gene, they do not secrete IL-15 activity. These observations suggest that both cytokines can differentially regulate T cells, e.g. T cell functions relevant to the control of cell cycle progression and apoptosis, and/or that they can stimulate different T cell subsets. Moreover, IL-15 may potentiate IL-2-driven T cell responses.