Mokola virus, one of the six genotypes within the Lyssavirus genus of the Rhabdoviridae family, is believed to be exclusive to the African continent, where infections in various mammal species have been reported. After an isolation of Mokola virus at Umhlanga on the east coast of South Africa in 1970, the virus was not reported in South Africa until its reappearance in 1995. Since then a total of six new isolates of the virus were made, three from the East London region in 1995 and 1996, two near Pinetown in 1997 and a further isolate in a residential suburb of the city of Pietermaritzburg, in 1998. These isolation sites are respectively about 500 km (East London region) and 23 to 60 km from the site of the 1970 isolation Phylogenetically the three isolates from the East London area were similar and could be distinguished from the four KwaZulu-Natal isolates, which formed a defined group of their own. The viruses comprising these two clusters were also found to be distant from another southern African isolate, made in 1982 in Zimbabwe, Mokola virus isolates thus conforms to a pattern of virus evolution strongly influenced by geographical determinants. In comparison to Rabies virus, of which at least two different biotypes are known and a vast array of different wildlife species contribute to its complex epidemiology on the sub-continent, Mokola viruses have only been isolated form one species, i.e. domestic cats, in South Africa. Nevertheless, the heterogeneity among the Mokola virus isolates is far greater than the degree of variation among the Rabies virus populations of the region.