Evidence was obtained that mononuclear phagocytic cells are the target cells for simian hemorrhagic fever virus replication. Using peritoneal macrophages from rhesus monkeys in an in vitro, 18 of 20 asymptomatic chronically infected patas monkeys were detected from coded samples. The two chronically infected patas monkeys not detected by the test, nevertheless, contained virus. This was determined by inoculating macrophage cultures with plasma from macaques dying as a result of inoculation with plasma from these chronically infected animals. in addition to virus found in chronically infected animals, all isolates of simian hemorrhagic fever virus tested previously described epizootics lytically infected rhesus monkey macrophages. These data suggested that the highly fatal nature of simian hemorrhagic fever in macaques was related to the extreme sensitivity of their mononuclear phagocytic cells to infection and lysis.