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Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position− 88 in the MxA gene promoter in self-limiting HCV infection (OR= 0.56; 95% CI: 0.35–0.8; P= 0.010) and in nonresponders to therapy (OR= 0.49; 95% CI: 0.25–0.95; P= 0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR= 0.22 95% CI: 0.07–0.67; P= 0.002). A polymorphism in the 3′-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR= 0.43; 95% CI: 0.21 …