The Epstein-Barr virus (EBV) major membrane antigen, gp350/220, was purified from expressing, genetically engineered Vero cells. The antigen, formulated either with alum or Freund's adjuvant, was inoculated into EBV infection-susceptible marmosets. After several injections, most of the marmosets developed anti-gp350/220 antibodies, and several exhibited virus-neutralizing activity. The immune response elicited by the alum-absorbed antigen proved to be protective upon virus challenge of the inoculated animals. Protection did not correlate with the presence of neutralizing antibodies.