One of the main characteristics of HIV-1 infection is persistent systemic immune activation. This immune activation and dysregulation is characterized by a specific pattern of cytokine production, expression of membrane activation molecules on the cells of the immune system, and changes in the levels of several immune parameters in blood. Therefore, the aim of the present work was to evaluate the effect of a Taq1 polymorphism in the 3'UTR of the IL-12B gene at position -1188 (A/C) and the biallelic polymorphism in the first intron of IFN-gamma at position +874 (T/A) on HIV-1/AIDS among north Indian population. IL-12B and IFN-gamma gene polymorphisms were studied in 300 patients with HIV-1/AIDS and an equal number of negatively diagnosed controls of the matched age, using DNA-based polymerase chain reaction with sequence-specific primers and restriction digestion. The allelic as well as genotypic frequencies of interleukin-12B gene polymorphisms did not significantly differ between HIV-1/AIDS patients and negative healthy controls. A statistically significant correlation was found between IFN-gamma polymorphism and the risk of the disease. The present study suggested that individuals with mutant homozygous IFN-gamma AA genotype were at risk of HIV-1/AIDS (OR = 1.88, 95% CI 1.14-3.10, P = 0.008).