Two Epstein-Barr virus (EBV) types are known, EBV1 and EBV2, which possess substantially diverged alleles for latency genes EBNA-2, EBNA-3A, EBNA-3B and EBNA-3C but are thought to be otherwise similar. We report the first complete EBV2 genome sequence, for strain AG876, as 172,764 bp. The sequence was interpreted as containing at least 80 protein coding genes. Comparison with the published EBV1 sequence demonstrated that the two sequences are collinear and, outside the known diverged alleles, generally very close. The EBNA-1 gene was identified as another diverged locus, although its variation is believed not to correlate with EBV type. Patterns of substitution between the two genomes presented a wide spectrum of classes of change. No evidence was seen for involvement of B-cell-specific hypermutation systems in generation of the diverged alleles. Overall, genomic comparisons indicated that the two EBV types should be regarded as belonging to the same virus species. (c) 2006 Elsevier Inc. All rights reserved.