EBV has been sporadically described as a cause of infectious mononucleosis (IM) following transfusion of blood (TOB) but systematic studies to establish the risk of EBV infection (inf), both silent and overt, from TOB have not been performed. We undertook a pilot study to ascertain whether children undergoing open heart surgery (OHS) requiring TOB developed EBV inf. 44 children, 3 mos-15 yrs (median 5 yrs), were enrolled and tested for EBV-specific antibodies at entry and 1,4,12,26, and 52-78 wks after surgery. 29(66%)/44 were seroneg; 3/29 (10%) died and 5 (17%) have been lost to follow up. These seroneg children received 1-5 TOB (mean 3.65 units); 89% of the 106 units were seropos and each seroneg child was exposed to at least 1 seropos unit. Of the 21 seroneg (all followed >6 mos), 17(81%) remained susceptible and 4(19%) seroconverted, including a 15 y/o who developed IM and 3 children 6-18 mos old with asymptomatic inf. Two asymptomatic inf probably occurred 2-6 mos after surgery and the other >6 mos postoperatively. We conclude that children undergoing OHS are at risk of acquiring EEV from TOB as they are likely (a)to be susceptible and (b)to receive seropos blood (containing EBV-infected lymphocytes). Additionally, the detection of EBV inf in 4 children following OHS suggests a need for larger, controlled studies to determine whether the source of such postoperative infections is TOB.