IL-15 uses two distinct receptor and signaling pathways. In T and NK cells, the type 1 IL-15 receptor includes the IL-2/15R subunit shared with IL-2, the c subunit shared with IL-2, IL-4, IL-7, and IL-9, as well as an IL-15-specific receptor subunit IL-15R. Thus type 1 receptor uses a JAK1/JAK3 and STAT3/STAT5 signaling system. Mast cells respond to IL-15 with a type 2 receptor system that does not share elements with IL-2R but uses a novel 60±65 kDa IL-15RX subunit. This type 2 receptor signaling involves JAK2/STAT5 activation. In addi- tion to the other functional activities in immune and nonimmune cells, signaling through the type 1 IL-15 receptor plays a pivotal role in the development, survival, and activation of NK cells.