Lymphocytes bearing γδ T cell receptors (1CR) constitute a minor subpopulation of human peripheral blood lymphocytes. Their role and function during microbial infections are largely unknown. In 10 patients with Epstein-Barr virus-induced infectious mononucleosis, the γδ TCR-expressing T cell population expanded during the acute phase. These cells were largely δTCS1^-, CD4^-, and CD8^- but expressed activation antigens such as human leukocyte antigen-DR and CD38. The convalescent phase of infectious mononucleosis was characterized by a relative persistence of γδ T cells. Together these data suggest a possible role of γδ T cells in the control of primary Epstein-Barr virus infection in humans.