We have used latent infection with the human herpesvirus Epstein-Barr virus to track the dispersal of memory B cells from the mucosal lymphoid tissue of Waldeyer's ring (tonsils/adenoids). EBV is evenly distributed between the memory compartments of Waldeyer's ring and the peripheral blood. However, it has an approximately 20-fold higher preference for Waldeyer's ring over the spleen or mesenteric lymph nodes. These observations are consistent with a model whereby the virus preferentially establishes persistent infection within memory B cells from Waldeyer's ring. The virus then colonizes the entire peripheral lymphoid system, at a low level, by trafficking with these memory B cells as they circulate through the body and back to Waldeyer's ring. This pathway may reflect that of normal memory B cells derived from nasopharyngeal and other mucosal lymph nodes.