In 1957, a fatal disease occurred among monkeys in a forested area of Shimoga District, Karnataka State, India. Concurrently, there was an outbreak of febrile, occasionally fatal illness among people living in the vicinity. The disease was caused by a new tick-borne flavivirus belonging to the Russian spring-summer encephalitis complex of viruses. The early clinical description of the disease included severe cases with hemorrhagic manifestations, including intermittent epistaxis, hematemesis, melena, and frank blood in the stools. Pathologic and hematologic investigations emphasized similarities with Omsk hemorrhagic fever. Two years later there was a shift in clinical emphasis from hemorrhagic to neurologic complications; this could have resulted from the special interests or bias of the principal investigator or the changing patterns of intercurrent infections. Clinical, clinicopathologic, hematologic, and hemostatic features of Kyasanur Forest disease (KFD) are described, particularly in relation to IgE as a cofactor in the immunopathology of KFD and possibly of other hemorrhagic fevers.