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Our group has previously described five different size alleles of an interferon (IFN)-γ microsatellite. Analyzing this polymorphism, this study correlated high IFN-γ production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status.Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-γ and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups.The genotype associated with high IFN-γ production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-γ genotype group, compared with 44.4% in the low IFN-γ group. Requirement for antithymocyte globulin therapy was greater in the high IFN-γ group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-γ genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-γ genotype had a 61% incidence of rejection compared with only 20% in the low IFN-γ genotype patients (OR=3.06). Graft survival was similar between the two groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-γ genotype patients had serum creatinine levels above 200 μmol/L compared with only 14.3% of the low IFN-γ genotype recipients at 5 years after transplantation (P =0.05). The high IL-10 genotype was shown to be associated with better graft function at 5 years (75 vs. 50%, P =0.09).In this study we have shown that high producer genotype for IFN-γ may have an influence on acute rejection of kidney transplants, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.