IFN-γ is a cytokine with pleiotropic functions that participates in immune and autoimmune responses. The lack of IFN-γ is known to delay the development of autoimmune diabetes in nonobese diabetic (NOD) mice. Splenocytes from diabetic NOD and IFN-γ knockout (KO) NOD mice transfer diabetes into NOD recipients equally well. However, adoptive transfer of diabetogenic T cells from NOD mice into NOD. IFN-γ-KO or NOD mice lacking β-chain of IFN-γ receptor (NOD. IFN-γRβ-KO) appeared to be much less efficient. We found that IFN-γ influences the ability of diabetogenic cells to penetrate pancreatic islets. Tracing in vivo of insulin-specific CD8+ T cells has shown that homing of these cells to the islets of Langerhans was affected by the lack of IFN-γ. While adhesion of insulin-specific CD8+ cells to microvasculature was normal, the diapedesis was significantly impaired. This effect was reversible by treatment of the animals with rIFN-γ. Thus, IFN-γ may, among other effects, influence immune and autoimmune responses by supporting the homing of activated T cells.