Interleukin-15 (IL-15) is a novel cytokine displaying biological activities that overlap those of interleukin-2 (IL-2). Like IL-2, IL-15 has been shown to be capable of stimulating the proliferation of human natural killer cells and PHA-treated T lymphocytes and of generating cytotoxic activity in stimulated lymphocyte populations. Using primary murine lymphocytes as a model in the present study, we have investigated the effects of IL-15 on the induction of the expression of mRNAs encoding different lymphocyte cytolytic mediators and the enhancement of cytolytic activities. Using reverse transcription-polymerase chain reaction analysis, both IL-15 and IL-2 have been shown to induce the expression of mRNAs for perforin, granzymes A and B, interferon-gamma, and Fas ligand in primary murine splenic lymphocytes. The induction effect of IL-15 has been shown to be at least partially independent of cell proliferation. Although IL-15 and IL-2 appear to be comparably effective in inducing the expression of cytolytic mediator mRNAs, the former is less potent in eliciting functional cytolytic activity in stimulated lymphocyte populations. The inadequate cytolytic activity of IL-15-stimulated lymphocytes may in part be due to the less efficient production of cytolytic mediator proteins, e.g., perforin and granzyme A, in these cells.