Serial serum specimens from forty-five patients with infectious mononucleosis were tested by indirect immunofluorescence for the presence of antibody against a herpeslike virus (HLV) first found in continuous cell lines established from biopsy specimens of Burkitt tumors. Most patients had detectable levels of anti-HLV antibody in the first specimens tested; however in several no antibody was demonstrable early in their illness but titers of 1:10 or greater developed after a few weeks. Peak titers ranged from 1:10 to 1:640. They were more variable than those found in serum from African children with Burkitt tumor, all of whom had high levels of anti-HLV antibody. During convalescence, titers tended to remain elevated and even to rise. Of an age- and sexmatched control group 55 per cent had demonstrable antibody to HLV in their serum as did 76 per cent of a group of fifty persons associated in the study of leukemia and lymphoma. HLV could be demonstrated in thirteen of sixteen long-term leukocyte cultures isolated from the peripheral blood of nine patients with infectious mononucleosis. The data available so far are not sufficient to permit us to draw any firm conclusions about the role HLV may play in the pathogenesis of infectious mononucleosis; alternative explanations for present findings can be offered.