The cytokine interleukin (IL)-15 shares several activities with IL-2. Both cytokines induced expression of cell-surface IL-2R alpha (CD25) on freshly isolated human peripheral blood mononuclear cells (PBMC) in the absence of other exogenous stimuli. They also stimulated the release of soluble IL-2R alpha and induced proliferation of these cells in 1-week cultures in a time- and dose-dependent manner. Recombinant IL-7 could also induce the expression of CD25, although sIL-2R alpha was released at only low levels. In monocyte-depleted PBMC the sIL-2R alpha release was minimal. When isolated T cells or non-T cells were stimulated by rIL-15 or rIL-2, cell surface CD25 was expressed, but released sIL-2R alpha was undetectable. On stimulation with rIL-15, more than 80% of all natural killer cells expressed CD25 and more CD8br+ lymphocytes were positive for CD25 compared to stimulation by rIL-2. These results may be clinically relevant because several diseases are associated with high serum levels of sIL-2R alpha which may he not only due to IL-2 but also due to IL-15 stimulation.