The lnterleukln-2 (IL-2) receptor y chain (IL-S&) is a component of high and Intermediate affinity IL-2 receptors that is required to achieve full ligand binding affinity and Internalization. We have localized the IL-PRy gene to humanchromosomeXql3. Genetic llnkage analysis Indicates that the IL-PRY gene and the locus for X-linked severe combined lmmunodeficlency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation in his IL-2Rl gene resulting In a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID Is associated wlth mutations of the IL-PRY gene product. Since XSCID Is characterized by absent or markedly reduced numbers of T cells, our findings lmply that IL-2Ry plays a vital role In thymlc maturation of T cells. These results also have important lmplicatlons for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID.