Atypical lymphocytes (ATL) appear in the circulation of a large proportion of patients during the first week following a blood transfusion. In order to determine the source of these ATL, cytogenetic studies were performed on the peripheral blood leukocytes of ten adult patients who received fresh blood from donors of the opposite sex. Nine of the ten patients had spontaneously dividing mononuclear cells of the recipient or host karyotype circulating during the latter part of the first week after transfusion. In two patients, the spontaneously dividing cells were of donor as well as of host origin. Six patients had circulating phyothemagglutinin-responsive lymphocytes of the donor karyotype noted from 1–7 days after transfusion. These findings lend support to our hypothesis that the increase in circulating atypical lymphocytes seen 1 wk after transfusion represents the counterpart in vivo of the in vitro mixed leukocyte reaction. The dividing donor cells may represent a subclinical graft-versus-host reaction.