Our laboratory has identified an X-linked severe combined immunodeficiency (XSCID) in dogs that is the result of mutations in the common gamma chain (gammac) subunit of the interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 receptors. Canine XSCID, unlike genetically engineered gammac-deficient mice, has a clinical and immunologic phenotype virtually identical to human XSCID, suggesting species-specific differences exist in the role of the gammac and its associated cytokines in mice in comparison to their role in humans and dogs. This review compares and contrasts thymopoiesis and postnatal T cell development in gammac-deficient (XSCID) dogs raised in a conventional environment, with gammac-deficient dogs raised in a gnotobiotic environment. Therapy to accelerate T cell regeneration following hematopoietic stem cell transplantation or gene therapy is also discussed.