Objective: To evaluate the serologic reactivities in patients infected with different hepatitis C virus (HCV) genotypes to four HCV proteins that are components of the second-generation recombinant immunoblot assay. Material and Methods: Serum samples from 36 patients with chronic HCV infection were obtained, RNA was extracted by using chaotropic lysis and isopropanol precipitation, Reverse-transcriptase polymerase chain reaction of the NS-5 region was performed, followed by automated single-pass dideoxy sequencing of desalted amplification products, Classification of isolated HCV subtypes was based on Simmonds' system, All samples were tested for antibodies to proteins 5-1-1, C100-3, C33c, and C22-3 with the second-generation recombinant immunoblot assay, Results: Reactivity to protein 5-1-1 was significantly lower for patients with genotypes 2b and 3a than for those infected with HCV types 1a or 1b (P<0.05), Antibody reactivity to the C100-3 protein was also reduced in patients infected with HCV types 2b and 3a. Conclusion: These data indicate that the genotype-dependent differences in serologic reactivities are substantial among patients with chronic HCV infection.