Background: Episodes of acute rejection represent an important risk factor for the development of chronic allograft nephropathy. We explored whether certain cytokine gene polymorphisms in renal transplant recipients may be useful markers for susceptibility to allograft rejection. Interleukin 8 (IL8) -251 T>A and interferon gamma (IFNG) +874A>T gene polymorphisms were correlated with allograft outcome in renal transplant recipients. Methods: Genotyping was done by amplification refractory mutational system-polymerase chain reaction (ARMS-PCR) in 264 healthy controls and 296 renal transplant recipients categorized into 235 non-rejecters and 61 rejecters. Results: IL8 -251AA genotype was associated with 2.7-folds increased risk for allograft rejection in recipients experiencing rejection episodes as compared to non-rejecters (OR = 2.70, P = 0.032). Cox proportional analysis revealed > 2-folds increased susceptibility for allograft rejection (HR = 2.38, P = 0.010) in IL8 -251AA recipients. Kaplan-Meier analysis also demonstrated lower mean time to first rejection episode for IL8 -251AA recipients (23 months) as compared to TT recipients (30 months) (log rank P = 0.022). No association of IFNG +874A>T was observed with allograft rejection, however, an increasing trend towards immunosuppressant toxicity was observed in patients with +874TT genotype at one month post transplantation. Conclusion: Thus, IL8 -251AA genotype may serve as potential predictor of allograft outcome in our North Indian cohort of renal transplant recipients. © 2009.