Nucleotide sequence analysis of a 200-bp region of the nucleoprotein (N) gene of rabies virus differentiated unique genetic groups of rabies virus from samples collected in areas where dog rabies is enzootic in Asia, Africa, Europe, and the Americas. Patterns of nucleotide sequence identified for an outbreak area were conserved in samples collected over three decades. Epidemiologic relationships among isolates were determined by patterns of conserved nucleotide sequence, and the degree of sequence divergence between samples from separate outbreak areas were measured. This approach suggested that a historical reconstruction of events leading to the introduction of rabies into an area would be possible. In this broader view of rabies epidemiology, the cultural legacy of European exploration and colonization may have also included zoonotic disease.