Laboratory mice are born lymphopenic and demonstrate lymphopenia-induced proliferation that generates memory T cells, yet they are prone to immunologic tolerance. Here we tested whether these fundamental immunologic observations apply to higher animals by studying the immune system of infant baboons. Using flow cytometry of the peripheral blood cells, it was found that baboons are born relatively lymphopenic and subsequently expand their initially naïve T cell pool with increasing numbers of memory T cells. After transplantation of an artery patch allograft or xenograft, non-immunosuppressed recipients readily mounted an immune response against donor-type antigens, as evidenced by mixed lymphocyte reaction. Immunosuppression with anti-thymocyte globulin (ATG), anti-CD154 mAb, and mycophenolate mofetil prevented T cell-mediated rejection. After lymphocyte depletion with ATG, homeostatic T cell proliferation was observed. In conclusion, the baboon proved a suitable model to investigate the infant immune system. In this study, neonatal lymphopenia and expansion of the memory T cell population were observed but, unlike mice, there were no indications that infant baboons are prone to T cell tolerance. The expansion of memory T cells during the neonatal period or after induction therapy may actually form an obstacle to tapering immunosuppressive therapy, or ultimately achieving immunologic tolerance. © 2011 European Society for Organ Transplantation.