Interleukin-15 (IL-15), a product of monocytes and other cells, has biological activities similar to those of IL-2, including growth stimulation of activated T cells, induction of cytolytic effector cells, and B-cell costimulation for proliferation and lg production. We report that IL-15 at optimal concentrations rapidly induced memory (CD45RO+) CD4+ and CD8+ T cells and naive (CD45RO-) CD8+ T cells to express the CD69 activation marker followed by proliferation. By contrast, IL-15 failed to induce naive (CD45RO-) CD4+ T cells to express CD69 or to proliferate. Similar findings were obtained with IL- 2. Unlike the other T-cell subsets, CD4+ T cells with a naive phenotype expressed little or no IL-2R beta chain, a shared component of the IL-2 and IL-15 receptors required for receptor function. A monoclonal antibody to the IL-2R beta chain, Mik beta 1, reduced CD69 expression and proliferation in CD4+ memory, CD8+ memory, and CD8+ naive T cells activated by IL-15. These results confirm the biological similarities of IL-2 and IL-15. They further document that the pool of naive CD4+ cells, unlike the pool of memory CD4+, memory CD8+, and naive CD8+ cells, is not regulated directly by the T-cell growth factors IL-2 or IL-15.