SummaryThe addition of interleukin‐2 (IL‐2) to lymphocyte cultures from acute infectious mononucleosis (IM) donors dramatically increased the incidence of regression in such cultures and resulted in the emergence of an IL‐2 dependent, CD3 Epstein‐Barr virus nuclear antigen (EBNA)‐negative cell population. Corresponding cultures seeded in the absence of IL‐2 rarely regressed and were quickly dominated by IL‐2 independent, CD3‐negative, EBNA‐positive cells. Lymphocyte cultures from Epstein‐Barr virus (EBV) seropositive donors showed enhanced regression in the presence of IL‐2 but failed to regress after the removal of the E‐rosetting population. Cultures from EBV‐seronegative donors showed no evidence of regression in the presence or absence of IL‐2. E‐rosetting cells isolated from cultures from acute IM donors that had been cultured in the presence of IL‐2 lysed autologous and allogeneic lymphoblastoid cell lines.