predict successful therapy for HCV. Conversely, interleukin 10 (IL-10), a cytokine of Th2 response antagonizes antiviral effects of Th1 response mediated mainly by INFg production. Therefore, IL-10 could interfere in the response of patients to pegIFN-a/RBV. Our aim was to associate the levels of IL-10 at the end of pegIFNa/RBV treatment with IL28B polymorphisms. Methods: Patients infected with HCV (n =487) and blood donors (n = 234) were genotyped for IL28B at rs12979860. Treatment was done with pegIFN-a/RBV either 24 or 48 weeks. Patients were grouped in Sustained Virological Responder (SVR) and NonResponder or Relapse (NR/RL). TAQMAN probes determined the IL28B SNPs at rs12979860, giving CC, CT or TT genotypes. Serum IL-10 was measured in 143 out of 487 patients using ELISA (R&D Systems, Inc.). Statistics employed qui-square test, 95% of CI, t-Student test or Mann–Whitney was used when appropriated, and p-value was considered significant when <0.05. Results: The frequency of CT/TT was higher in HCV 75% vs. 68% blood donors group (p =0.02, OR 1.4 IC 1.00–1.96) and SVR group was associated with IL28B CC genotype (p =0.02 OR 2.2 IC 1.15–4.2). CC-SVR group showed lower IL10 (8.5±3.4 pg/mL) compared to the other groups CC-NR/RL (16.6±10.9 pg/mL), CT/TTNR/RL (16.9±10.9 pg/mL) and CT/TT-SVR (14.1±9.1 pg/mL) with pvalues 0.009, 0.011 and 0.003 respectively. The IL-10 didn’t differed among CC-NR/RL and CT/TT-SVR or CT/TT-NR/RL. Slight difference was observed between CT/TT-SVR and CT/TT-NR/RL (p = 0.09). Confounding variables such as HCV genotype, METAVIR fibrosis scale, age and sex were not statistically different between groups. Forty percent of CC showed IL-10 at 8.5 pg/mL, while 23% CT/TT patients presented levels of IL-10 at 14.1 pg/mL. Conclusions: IL10 levels were lower in IL28B CC-SVR vs. CT/TT-SVR, suggesting that the IL-10 decrease effect caused by pegIFN-a/RBV seem to be more sustained in CC genotype, reflecting higher SVR rate in this group. Also, the results showed a higher CC genotype frequency in health blood donors compared to HCV group, which may be related to protection to infection as previously described.