For the first time we have characterized an unoccupied site of Epstein-Barr (EBV) virus integration in a lymphoblastoid cell line, RGN1. The site of integration is about 1.5 kb downstream from the gene encoding the heavy chain constant alpha 1, specifying immunoglobulin A (IgA). Sequence and Southern analysis allowed us to hypothesize that integration occurred via a double exchange involving the viral latent origin of DNA replication (oriP) and the human DNA. The region involved in the integration is transcribed into poly(A)+ RNA in all the tested lymphoid lines, but not in the RGN1 line. We suggest a mechanism of integration primed by interactions between oriP and cell ori and its potential role in the establishment and/or evolution of EBV-carrying lines.