Rheumatoid arthritis is a chronic autoimmune disorder associated with altered expression of pro- and anti-inflammatory cytokines in the affected tissues. The aim of this study was to investigate the association between promoter polymorphisms of TNFalpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position -308 and -863 of TNF gene and -819/-592 and -1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF -308A was less prevalent among the patients (1.7%) than controls (4.9%; p = 0.01, OR: 0.32, 95% CI: 0.13-0.76). Among female patients, IL-10 -592A allele associated with higher baseline disease activity scores (5.77 +/- 1.99) than -592C (5.57 +/- 1.19; p = 0.04). Female patients carrying allele A of TNFalpha -863 had earlier age of onset of RA (33.99 +/- 9.6 years) than those with allele C (36.15 +/- 11.21 years; p = 0.043). In conclusion, allele A at TNFalpha -308 locus provides protection against RA in North Indian population while another TNF allele A at -863 position had weak association with earlier onset of disease in female patients. On the other hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at -819/-592A was associated with higher disease activity scores at baseline.