During the autumn of 1999 (mid-August–late September), an outbreak of hemorrhagic disease in white-tailed deer (Odocoileus virginianus) caused by epizootic hemorrhagic disease virus serotype 1 (EHDV-1) occurred along the east coast of the United States from Georgia to New Jersey. An EHDV-1 epizootic of such magnitude had not been described in this region since 1975. To determine the genetic relatedness among the 1999 viruses, as well as among additional EHDV-1 isolates from the eastern and western United States, portions of the S10 and L2 gene segments were sequenced and compared utilizing phylogenetic analyses. Nearly all of the 1999 eastern isolates were identical in nucleotide sequence at one or both loci. Additionally, confirmed cases of EHDV-1 in white-tailed deer occurred in a south (Georgia)-to-north (New Jersey/Virginia) progression over a short period of approximately six weeks. Taken together, these results indicate that this outbreak resulted from the spread of a single viral strain. The phylograms derived from analysis of the entire sample set displayed eastern and western region–specific clusterings (topotypes), as well as an eastern versus western difference in branch lengths, which may reflect the influence of epizootic versus enzootic transmission patterns on viral genetic diversity.