Granulocyte colony-stimulating factor (G-CSF) can be administered to healthy donors to mobilize CD34+ peripheral blood progenitor cells (PBPC) for transplantation into HLA-matched allogeneic recipients. Current clinical trials report a similar incidence and severity of acute graft-versus-host disease (G-VHD) compared with transplantation of allogeneic bone marrow (BM) despite the infusion of 1-2 more logs of T lymphocytes. An overview of modulation of T cell function both in animal models and in humans receiving G-CSF is provided. The experimental evidence summarized in the present article highlights a powerful immunoregulatory action exerted by G-CSF, consisting of (1) increase in soluble immunoregulatory cytokines, (2) inhibition of lymphocyte proliferation, and (3) induction of lymphocyte partial activation after mitogenic challenge. These findings offer an experimental background for promising and innovative approaches to cytokine therapy.