The description of IL-10 as an immunosuppressive cytokine that inhibits numerous T-cell and antigen-presenting cell functions has led to the investigation of the role of IL-10 in graft acceptance and rejection, in both manipulated and unmanipulated experimental systems. Recent results suggest a complex interaction of IL-10 with other cytokines and numerous cell types. Although IL-10 is not a simple immunosuppressive molecule, manipulation of its actions may be a useful approach for prolonging graft survival and preventing rejection.