This study investigates the role of interleukin (IL)-7 in lymphocyte development and function by creating IL-7 gene-deficient mice. The results show that these mice exhibit severe lymphopenia, with reduced numbers of both B and T cells in peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis is blocked at the transition from pro-B to pre-B cells, and thymic cellularity is reduced by 20-fold. Splenic T cellularity is reduced by 10-fold, and splenic B cells show an abnormal population of immature B cells. Despite these reductions, the remaining lymphocytes show normal responsiveness to mitogenic stimuli. These findings demonstrate that IL-7 is essential for proper T and B cell development and function, highlighting its unique and nonredundant role among cytokines. The study also suggests that other cytokines that bind to the IL-2 receptor gamma chain may play a role in lymphocyte development, as seen in IL-7Rα-deficient mice.This study investigates the role of interleukin (IL)-7 in lymphocyte development and function by creating IL-7 gene-deficient mice. The results show that these mice exhibit severe lymphopenia, with reduced numbers of both B and T cells in peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis is blocked at the transition from pro-B to pre-B cells, and thymic cellularity is reduced by 20-fold. Splenic T cellularity is reduced by 10-fold, and splenic B cells show an abnormal population of immature B cells. Despite these reductions, the remaining lymphocytes show normal responsiveness to mitogenic stimuli. These findings demonstrate that IL-7 is essential for proper T and B cell development and function, highlighting its unique and nonredundant role among cytokines. The study also suggests that other cytokines that bind to the IL-2 receptor gamma chain may play a role in lymphocyte development, as seen in IL-7Rα-deficient mice.