The postulated role of macrophages in the primary infection of human lymphocytes by Epstein-Barr virus (EBV) was examined. Macrophage removal had no effect on the blastogenic response but slightly reduced the percentage of EBNA-positive cells induced by the B 95-8 virus strain. Both the rate of DNA synthesis and the appearance of EBNA-positive cells could rather be related to the number of B cells in the infected populations. Macrophages are thus not required for the initiation of EBV-induced lymphocyte transformation.