Graft-versus-host-disease (GVHD) is a major complication following bone marrow transplantation (BMT) with a high mortality rate. Therefore it is important to further understand the human immune response in the development of GVHD. Humanised mice represent an ideal model to investigate GVHD as mice injected with human peripheral blood mononuclear cells (hPBMCs) are known to develop GVHD at 4-6 weeks post-injection. NODSCIDIL2Rγ-/- (NSG) mice injected with hPBMCs showed similar levels of engraftment of human CD45+ T cells at 3 weeks post-injection. Engrafted human cells are predominantly human CD3+ T cells and include both CD4+ and CD8+ T cells. The majority of engrafted humanised mice develop GVHD symptoms including weight loss and increased clinical scores. Despite similar levels of human cell engraftment, some mice do not develop GVHD, potentially providing important insight into GVHD development. Mice with GVHD show a higher splenic CD4:CD8 ratio compared to engrafted mice without GVHD. Increased human IFN-γ was observed in the serum of mice with GVHD compared to mice without GVHD. Similar levels of human cytokines (IL-6, TNFα, IL-2, IFN-γ) were observed in the spleen of humanised mice with or without GVHD. However, significantly increased IL-17A expression was observed in the spleen and liver of humanised mice with GVHD. This study indicates an important role for human IFN-γ and IL-17A in the development of GVHD in humanised mice.