Hepatitis C virus demonstrates a high degree of variability HCV isolates have been classified into at least six genotypes, according to the percentage of nucleotide sequence homology. Geographical differences in the distribution of virus genotypes are well documented. Types 1, 2 and 3 are the major types observed in Japan, Western Europe and North America; type 4 has been found in Central and Northern Africa and in the Middle East; type 5 has been described in South Africa, type 6 in South-East Asia. The relative prevalence of these genotypes varies between different regions. In the Indian subcontinent, subtype 1b seems to be the most prevalent type, but many isolates have been described, related to genotype 3, in Northern and Southern India, Pakistan and Nepal. HCV genotypes may have potential clinical implications: a) the association with the severity of liver disease is still controversial; b) the association between some genotypes, particularly 1b, and a poor response to interferon alpha therapy has been well established; c) genotyping may be useful for identifying some unusual modes of transmission of the virus. Finally, the variability of HCV virus has major implications for the design of new vaccines strategies since there is no cross-protection between different HCV types.