In our study we investigated the role of the polymorphisms in the first exon of MBL2 gene in the susceptibility to HCV infection and disease progression in a Northeastern Brazilian population. One hundred and eleven patients seen at the Gastroenterology Service of the Oswaldo Cruz Hospital of the University of Pernambuco were included in this study. A total of 165 unexposed, uninfected individuals matched for place of origin were employed as healthy controls. MBL2 genotyping was performed by using a melting temperature assay. The 0 allele was significantly more frequent in the HCV positive group than the healthy controls (34% vs. 20%, p<0.01, respectively) and was associated to an increased risk of HCV-1 infection (O.R.=2.1; C.I. 1.41-3.19). Also genotypes frequencies were significantly different in HCV positive subjects when compared to healthy controls with the 00 and A0 genotypes being significantly overrepresented in HCV infected subject (15% and 37%, respectively) as compared to healthy subjects (6% and 27%, respectively, p<0.01 ) Allele and genotypes frequencies were also evaluated in HCV infected subjects according to their response to pegylated-INFalpha/riboviron therapy. There was a trend for HCV positive responders vs. non-responders to be 0 allele positive and a similar trend was observed for the MBL2 A0 and 00 genotypes, but neither of these reached statistical significance. Our findings indicate that MBL might represent an important antiviral molecule having a protective role in the first stages of HCV infection, as shown by the increased frequency of wild-type alleles in control population as compared to the infected group.