Four groups of hamsters were infected sequentially with various combinations of Arumowot, Chagres, and Gabek Forest viruses. Following each infection, the survival, level of viremia, and immune response of the animals were monitored. All of the agents produced viremia in the hamsters, regardless of the order of their administration. The antibody response, as measured by plaque reduction neutralization test, was monotypic even after two consecutive phlebovirus infections. Arumowot and Chagres viruses produced nonfatal infections in adult hamsters, which were characterized by viremia of several days duration and subsequent antibody formation. In contrast, Gabek Forest virus produced a fulminating and rapidly fatal disease in phlebovirus nonimmune animals. In hamsters previously infected with Chagres and/or Arumowot viruses, Gabek Forest infection was less severe, indicating some degree of cross-protection. The degree of cross-protection was in part related to the sequence of previous phlebovirus infections. No evidence of immune enhancement or other immunopathologic events were observed in the animals.