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Rabies is an ancient disease and a fearsome one. Although it may not have the economic or public health importance of some other infectious diseases, few are so well known or carry the same emotional impact. Mainly transmitted by the bite of an enraged animal, and with practically no hope for recovery among those afflicted, it has provided the substance of stories and legends throughout the ages. The pioneering work of many 19th century workers, culminating in the development of the first rabies vaccines by Louis Pasteur, provided the ground work for the modern era in the study of rabies. Since then, and particularly in the last quarter century, considerable advances have been made in our knowledge of the nature of the infectious agent, its mode of transmission and pathogenetic mechanisms. Yet even today, much remains to be learned about the disease. For example, although effective vaccines exist for humans and other animals, there is still no known practical cure once the neurological disease symptoms develop. Markers of virulence have been mapped at the molecular level, but it is yet unclear as to how rabies virus actually exerts its pathological effects.