We explored the influence of the major CCR5 promoter or coding region variants as haplotypes and genotypes in a cohort of 250 chronically infected HCV patients receiving combined interferon/ribavirin therapy. No haplotype, including the D32-bearing haplo-type (G*2) reportedly associated in homozygotes with high HCV viral load (VL), showed a similar effect. Patients with genotype C/G*2 showed slightly lower median VL (p = 0.05). Neither the G*2 haplotype nor the C/G*2 genotype influenced viral dynamics during the initial 12 wk of treatment (p = 0.53). The genotype E/E was more frequent among sustained responders (15.5%) than non-responders (7.8%), and VL declined further among E/E homozygotes during the initial 12 wk of treatment, particularly those with HCV genotype 1 (p = 0.016). Differential receptor expression due to E/E homozygosity in HCV infection remains to be confirmed.