Allelic and genotype variations in the promoter region and the dinucleotide (CA)(n) repeat region in intron 1 of the interferon-g (IFNG) gene were analysed by direct sequencing and simple sequence length polymorphism (SSLP), respectively, in patients with acute hepatitis, and the prevalence was compared with that in healthy controls. Our results showed a significant association of heterozygous genotypes (CA)12/(CA)14 and (CA)12/(CA)16 in intron 1 of the IFNG gene in all categories of patients with acute hepatitis, classified on the basis of presence or absence of hepatitis E virus (HEV), in comparison with healthy controls. A novel polymorphism, -288 A-->T [from the translational start site, as per Human Genome Organization (HUGO) nomenclature], in the promoter region of the IFNG gene leading to a loss of the consensus domain for the interferon-stimulated response element (ISRE), as predicted by in silico analysis, was observed in 12.5% of patients with acute HEV infection. However, no significant difference in allele or genotype frequency was observed for the -288 promoter polymorphism, although the heterozygous -288 A/T genotype showed a moderate risk in patients with acute HEV infection alone (P = 0.29, odds ratio = 1.964, confidence interval = 0.46-8.45). The data suggest that the genotype at intron 1 of IFNG might affect susceptibility to acute hepatitis in HEV infection, which warrants further elucidation in a larger sample and also functional studies.