Crimean-Congo hemorrhagic fever (CCHF) came to modern medical attention in 1944–1945, when about 200 Soviet military personnel were infected while assisting peasants in war-devastated Crimea (Ukrainian SSR). Subsequent epidemics occurred in Astrakhan (1953–1968) and Rostov Oblasts (1963–1971) of USSR and in Bulgaria (1953–1973). There have been numerous lesser outbreaks in southern USSR and, in 1976, outbreaks in Pakistan. However, it was only in 1967, when Soviet workers first used the generally accepted newborn white mouse (NWM) inoculation technique for CCHF virus isolation and study, that the etiologic agent could be characterized antigenically, physiochemically, and morphologically. Collaboration in 1968 between the Soviet and American experts M. P. Chumakov and Jordi Casals demonstrated the serologically identical properties of virus strains from human CCHF patients and corpses, lower mammals, and ticks from Asian and European areas of the USSR and from Bulgaria, Congo (Zaire), Nigeria, and Pakistan. These results, confirmed and broadened in subsequent studies, enabled serological and other research tools to be developed for producing identifiable antibodies and antigens required in experimental procedures and seroepidemiological surveys and obtaining scientific evidence to demonstrate vector and reservoir species and virus dynamics in nature. CCHF virus, a member (without generic assignment) of the family Bunyaviridae, is the prototype of the CCHF serogroup, which also includes Hazara virus (from Ixodes redikorzevi parasitizing alpine voles in Pakistan). CCHF virus is enzootic in the Palearctic, Oriental, and Ethiopian Faunal Regions, chiefly in steppe, savanna, semidesert, and foothill biotopes where 1 or 2 Hyalomma species are the predominant ticks parasitizing domestic and wild animals. Presence of the virus has been demonstrated by isolations from humans, other mammals, and/or ticks, or by seroepidemiological survey results, in western and southern India, Pakistan, Afghanistan, Iran, Soviet Middle Asia (Turkmen, Uzbek, Kazakh, Kirgiz, and Tadzhik SSR), Transcaucasia (Armenian and Azerbaijan SSR), European USSR (Ukrainian and Moldavian SSR, Kalmyk and Daghestan ASSR, Astrakhan and Rostov Oblasts, and Krasnodar and Stavropol Regions of RSFSR), Bulgaria, Yugoslavia, Greece, Hungary, France, Senegal, Nigeria, Central African Empire, Zaire, Uganda, Kenya, Ethiopia, Tanzania, and Egypt. The ecologically atypical CCHF foci in Moldavian deciduous forest habitats of Ixodes ritinus and Dermatentor and Rhipicephalus species may represent a spillover phenomenon associated with environmental changes created by humans. CCHF virus is a true tick-associated arbovirus; it survives transstadially (from larva to nymph to adult) and interseasonally in several tick species and is transmitted transovarially to the F1 generation (in some cases to F2) in Hyalomma m. marginatum, H. marginatum rufipes, Dermacentor marginatus, and Rhipicephalus rossicus. Twenty-five tick species and subspecies have been reported to be CCHF virus reservoirs/vectors (the single record from an argasid, the birdparasitizing Argas persicus, remains to be confirmed). One-host ticks, Boophilus annulatus, B. microplus, B. decoloratus (and probably B. geigyi), appear to maintain intense virus interaction for many weeks or months between several tick species infesting artiodactyls (especially cattle). The 2-host vectors are Hyalomma m. marginatum, H. mmginatum turanicum and H. marginatum rufipes (and probably H. marginatum isaaci); they feed as immatures on birds, hares, or hedgehogs and, as adults, chiefly on artiodactyls (often also on humans). Other 2-host vectors, H. anatolicum anatolicum, H. detritum, and Rhipicephalus bursa, feed both as immatures and adults on artiodactyls. The H. marginatum complex, and H. a. anatolicum, are especially important in causing epidemics and outbreaks of human CCHF owing to their great numbers during certain periods and to their aggressiveness in seeking human hosts. Others, including 13 species of 3-host ticks [Haemaphysalis punctata, Amblyomma variegatum, Dermacentor (2 spp.), Hyalomma (5 spp.), and Rhipicephalus (4 spp.)], which generally seek human hosts less aggressively than the cited hyalommas, serve chiefly to maintain enzootic foci of CCHF virus circulation between ticks and wild and domestic mammals. Ground-feeding birds are often hosts of CCHF virus-infected ticks but birds apparently do not become viremic; the epidemiological role of these birds is to support populations of certain vector species and to disseminate these species intracontinentally and/or intercontinentally. CCHF epidemics have developed on a background of favorable climatic factors and environmental changes beneficial for survival of large numbers of hyalommas and of the hosts of both their immature and adult stages. The environmental changes have been wartime neglect of agricultural lands, introduction of susceptible military personnel or new settlers into infected foci, widescale collectivization of agriculture, changing pasture patterns, converting floodplains and marshy deltas to farmland and pastures, flood control, etc. Unusually severe winter-spring weather, resulting in decimation of Hyalomma populations and also of hosts of immature stages, appears to have been largely responsible for virus circulation to revert from epizootic (epidemic) to enzootic intensity. Humans become infected when bitten by infected ticks, or when crushing these ticks in their bare hands or shearing tick-infested sheep. Household and nosocomial cases resulting from contamination by bloody discharges from CCHF patients have been especially numerous and severe, often with great mortality, in villages and hospitals...