For many aspects of HCV research it would be very useful to have a set of replicons in which different genome regions are swapped by corresponding fragments from isolates of the same viral strain that might demonstrate different biological characteristics or bear evolving antigenic determinants. The isolates of the same HCV strain that are necessary for generation of such hybrid replicons might be obtained from a single-source outbreak of HCV infection. One such outbreak caused by the HCV AD78 strain, occurred in Germany due to infection of women by contaminated anti-D globulin. Using a sequential substitution of different segments of the Con1 replicon with the corresponding fragments from the AD78 strain of HCV, a set of chimeric Con1/AD78 subgenomic and full-length, AD78-based genomic replicons were generated. These replicons might be used as a new experimental tool for different aspects of HCV research, including studies of the nature of isolate-specific differences in interactions of the replicon with the host cell and analysis of the mechanisms of HCV resistance to antivirals. The newly generated full-length replicon can also be used for preparation of AD78-specific target cell lines, which may be invaluable for the analysis of the evolution of HCV cellular immune responses in the cohort of patients infected with the HCV AD78 strain.