Interleukin 15 (IL-15) and IL-2, which promote the survival of memory CD8⁺ T cells and regulatory T cells, respectively, bind receptor complexes that share β- and γ-signaling subunits. Receptor specificity is provided by unique, nonsignaling α-subunits. Whereas IL-2 receptor-α (IL-2Rα) is expressed together in cis with the β- and γ-subunits on T cells and B cells, IL-15Rα is expressed in trans on antigen-presenting cells. Here we present a 1.85-Å crystal structure of the human IL-15–IL-15Rα complex. The structure provides insight into the molecular basis of the specificity of cytokine recognition and emphasizes the importance of water in generating this very high-affinity complex. Despite very low IL-15–IL-2 sequence homology and distinct receptor architecture, the topologies of the IL-15–IL-15Rα and IL-2–IL-2Rα complexes are very similar. Our data raise the possibility that IL-2, like IL-15, might be capable of being presented in trans in the context of its unique receptor α-chain.