HUMAN herpesvirus type-6 (HHV-6) is a recently isolated herpesvirus which is highly prevalent in adult populations around the world 1-3. HHV-6 was first isolated from the peripheral blood of six individuals with lymphoproliferative disorders, two of whom were also infected with human immunodeficiency virus 1. HHV-6, in common with other herpesviruses, transactivates the HIV long terminal repeat linked to reporter genes 4,5 and has in addition been shown to accelerate HIV gene expression and CD4 cell death in cultures co-infected with both viruses 6. The virus is tropic for CD4+ lymphocytes 7,8 and persists in the peripheral blood of most seropositive individuals 9. We have now identified a gene in HHV-6 encoding a 490-amino-acid polypeptide homologous to the human adeno-associated virus type-2 (AAV-2) rep gene 10. This gene has an essential role in AAV-2 DNA replication 11,12, can trans-regulate homologous and heterologous gene expression 13-17, and inhibits cellular transformation 18. The acquisition of rep by HHV-6 could be due to natural transfer of genetic information between DNA viruses of eukaryotes and is likely to have important consequences for the life-cycle of HHV-6 and for host CD4 cell.