Between 1979 and 2000, foxes constituted the main reservoir of rabies in the Northern regions of Israel. Following the implementation of the fox-targeted oral vaccination programme (ORV) in 1998, rabies was eradicated from this area. Subsequently during 2004–2007, the biological and molecular characterization of the rabies isolates showed that stray dogs emerged as the main animal reservoir in Northern Israel while lower numbers of cases were reported in domestic animals. The virus isolates from foxes and dogs differed, in their molecular characterization, suggesting two distinct separate lineages. The transition from fox-mediated rabies to dog-mediated rabies is of great concern to public health because of the close contact between dogs and the human population.