We are studying the mechanisms of transformation of growth and cell surface properties of human and nonhuman primate lymphocytes following in vitro exposure to Epstein-Barr virus. We have found that in both humans and marmosets a small, resting lymphocyte bearing a receptor for complement is the cell most susceptible to transformation. In populations enriched in this cell type as many as 30% of virus exposed human cells will transform. Radiobiologic experiments indicate that the entire viral genome is needed for transformation. Studies with an inhibitor of DNA synthesis (BrdU) suggest that a period of viral DNA replication precedes stimulation of cellular DNA synthesis. EBV transformed marmoset cells lose a principal lymphocyte surface marker, the ability to form EAC rosettes, which is retained by transformed human cells. Studies in the current year will focus on 3 problems: quantitative studies of C3 binding and C3 activation on transformed human and marmoset cells, attempts to transform lymphocytes with biologically active DNA, and efforts to demonstrate viral DNA replication as an early event in transformation.