We found recently that patients with good graft outcome showed higher IFN-gamma and IL-2, and lower IL-10 plasma levels late post-transplant than early post-transplant. In this retrospective study, we compared cytokine plasma levels in 33 symptom-free outpatients with those of 33 renal transplant recipients with early acute rejection (EAR), 29 with chronic rejection (CR), and 34 healthy controls (HC) to assess whether there is evidence for Th1 activation late post-transplant in patients with good graft outcome. Cytokines were measured pre-transplant, one wk, one month, six months, one yr, and two yr after transplantation. Twelve and 24 months post-transplant, IFN-gamma plasma levels were significantly higher (p = 0.001; p = 0.001, respectively) and IL-4 plasma levels significantly lower (p = 0.028; p = 0.003, respectively) in patients with stable graft function than those in controls. Six, 12, and 24 months post-transplant, patients with stable graft function had similar IFN-gamma and IL-4 plasma levels as patients with successfully treated EAR (p = n.s.), and higher IFN-gamma (p = 0.013; p = 0.001; p = 0.0005, respectively) and lower IL-4 (p = 0.007; p = 0.417; p = 0.0001, respectively) plasma levels than patients with CR. These data suggest that increased plasma IFN-gamma and decreased plasma IL-4 late post-transplant might be involved in the induction of mechanisms that facilitate good long-term graft outcome.