Infection with Epstein-Barr virus (EBV) results in lifelong infection of B cells in the peripheral blood and in episodic shedding of virus from the oropharynx. We monitored patients treated with rituximab (anti-CD20 monoclonal antibody) and found that several had both no detectable B cells and no EBV in the blood but shed EBV from the throat. Although some models postulate that EBV traffics from the B cells in the blood to the throat, where it is subsequently shed, our findings indicate that circulating EBV in B cells is not necessary for the virus to persist in, and to be shed from, the oropharynx.