A T-to-A polymorphic sequence at position +874 in the interferon (IFN)-gamma gene (+874 IFN-gamma) might be associated with disease susceptibilities. To investigate the influence of +874 IFN-gamma polymorphism on the hepatitis C virus (HCV) viral load and the severity of liver disease, the single nucleotide polymorphism (SNP) was determined in 302 histologically proved chronic hepatitis C (CHC) patients [M/F: 180/122, mean age: 48.8 +/- 11.6 years, HCV genotype 1b: 147 (48.7%), liver cirrhosis: 29 (9.6%)] by using a polymerase chain reaction-sequence specific primers (PCR-SSP) approach. The distribution of genotypes for +874 IFN-gamma were T/T: 12 (4.0%), T/A: 71 (23.5%), and A/A: 219 (72.5%) and 27.5% (83/302) of patients' inherited T allele. The mean age of patients without A allele was significantly lower than other patients (41.7 +/- 11.3 vs 49.2 +/- 11.5 years, P = 0.028). Patients with the T allele of +874 IFN-gamma had a significantly higher rate of liver cirrhosis than patients with homozygote A allele (15.7% vs 7.3%, P = 0.028). By multivariate logistic regression analyses, T allele of +874 IFN-gamma and age were independent factors associated with cirrhosis (odds ratio/95% confidence interval: 2.519/1.128-5.622 and 1.065 /1.025-1.107, respectively). In conclusion, the authors' findings indicate that inheritance of +847 IFN-gamma polymorphism is associated with the cirrhosis in patients with CHC.