Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion/dele tion) and the 3-UTR (1188-A/C), which have been reported to influence IL-12 s ynthesis, are associated with the outcome of HCV infection. We analyzed 186 indi viduals with spontaneous HCV clearance, 501 chronically HCV infected patients, a nd 217 healthy controls. IL12B 3-UTR and promoter genotyping was performed by T aqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA amplification, respectively. The proportion of IL12B pro moter and 3-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype 1-infected patients with high baseline viremia c arrying the IL12B3-UTR 1188-Callele showed significantly higher sustained viro logic response (SVR) rates (25.3%vs. 46%vs. 54.5%for A/A, A/C and C/C) due to reduced relapse rates (24.2%vs. 12%vs. zero %for A/A, A/C and C/C). IL12B 3 -UTR 1188-C-allele carriers appear to be capable of responding more efficient ly to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be d emonstrated. Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion / deletion) and the 3 -UTR (1188-A / C), which have been reported to affect IL-12 s syndrome, are associated with the outcome of HCV infection. We analyzed 186 indiiduals with spontaneous HCV clearance, 501 chronically HCV infected patients, a nd 217 Healthy controls. IL12B 3-UTR and promoter genotyping was performed by T aqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA amplification, respectively. The proportion of IL12B pro moter and 3-UTR genotypes did not differ However, HCV genotype 1-infected patients with high baseline viremia c arrying the IL12B3-UTR 1188-Callele was significantly higher sustained viro logic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A / A , A / C and C / C) due to reduced relapse rates (24.2% vs. 12% vs. Zero% for A / A, A / C and C / C). IL12B 3 -UTR 1188-C-alleles carriers appear to be capable of responding more efficient ly to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be d emonstrated.