Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; The objective of this study was to analyse the possible role of HLA polymorphism of chronically infected hepatitis C virus patients in the response outcome to treatment with pegylated interferon-alpha plus ribavirin. To that end, 144 Brazilian patients infected only with genotype 1 of the virus were treated with pegylated interferon-alpha at 1.5 mu g kg-1 in conjunction with ribavirin (1000 mg if patient weight was 75 kg) for 48 weeks. The patients did not have concomitant HBV or HIV infections or liver disease, did not undergo previous antiviral treatment, and were followed up for 24 weeks after the end of treatment to assure they presented a sustained virological response. Patients were classified according to response to treatment in responsive (SVR), nonresponsive (NRS) and relapsers (REL). HLA class I and class II typing were carried out through PCR-SSO using Luminex technology. A statistically higher frequency of DRB1*11 patients was observed in the SVR group (39.6% vs. 14.3%P = 0.0012; Pc = 0.0156; OR = 3.94; 95% CI = 1.88.8). HLA-DQB1*03 patients were also more frequent in the SVR group, but the P value lost significance after Bonferroni correction (62.3% vs. 41.7%P = 0.024; Pc = 0.14, OR = 2.3; 95% CI = 1.144.60). HLA class II antigens can positively influence the response to treatment with pegylated interferon-alpha and ribavirin.