Four patients had severe diarrhea after undergoing stem cell transplantation. Human herpesvirus 6B (HHV-6B) DNA was detected in large intestine tissue specimens and in peripheral blood mononuclear cells. In situ hybridization was positive for HHV-6B DNA in the nuclei of goblet cells and, sometimes, in the histiocytes in the submucous region of the large intestine, which suggests that HHV-6B may infect and reactivate in these cells.