Introduction: Deficiencies in the common cytokine receptor γ chain (γ c ) result in abnormal lymphoid development and a severe immunodeficiency disease through the combined inactivation of the receptors for interleukins -2, -4, -7, -9, and -15. We have observed the development of secondary hematopoiesis with circulating hematopoietic progenitor cells in adult mice harboring a null mutation in γ c .Materials & Methods: in vitro CFU-C and in vivo CFU-Sd12 were used to determine the frequency of hematopoietic precursors.Results: The extramedullary changes were not secondary to bone marrow failure nor to inabilities to maintain circulating blood counts. An intrinsic defect in γ c hematopoietic stem cell commitment appeared unlikely, as fetal liver hematopoiesis was unaltered in γ c -embryos. Furthermore, the absence of NK cells in γ c -mice was not responsible for the observed hematopoietic changes. Peripheral TCRαβ T-cells from γ c -mice had an activated phenotype (CD62L l o , CD44 h i , CD69 h i ) and showed increased levels of transcripts for hematopoietic stimulating cytokines, including IL-3 and GM-CSF. An accumulation of these cells was further detected in the bone marrow, suggesting a role for residual T-cells in the enhanced hematopoiesis. Strikingly, the elimination of residual T-cells from γ c -mice (γ c -deficient mice on the nu/nu background) reduced splenic hematopoiesis to normal levels with absence of circulating hematopoietic precursors.Conclusion: These results implicate a deregulated TCRαβ T-cell population in the observed hematopoietic changes in γ c -mice, and emphasize the importance of γ c -dependent cytokine interactions in modulating mature T-cell responses.