Epstein-Barr virus (EBV) derived from the B95-8 line has transforming activity for cord blood cells, whereas virus derived from the P3HR-1 line lacks such activity. When the two viral preparations were compared for their ability to infect the same EBV-genome-negative lymphoblastoid cell line, BJA-B, they induced approximately the same number of EBV-determined nuclear antigen (EBNA)-positive cells. EBNA is compatibile with continued cell proliferation. No early antigen (EA)-positive cells appeared in the B95-8 virus-infected cultures, whereas P3HR-1 virus-infected cells went on to express EA. EA signals the entry of the cell into the lytic cycle. No late viral antigen (VCA) appeared and, as a consequence, the P3HR-1 virus infection became abortive. In contrast, the EBNA-positive cells induced by the B95-8 virus continued to divide over several weeks. These findings show that different EBV isolates may differ in their biological activity, probably due to their having different degrees of viral dependence on restrictive host cell controls.