Alan C Jackson MD (Dr. Jackson of the University of Manitoba has no relevant financial relationships to disclose.)
John E Greenlee MD, editor. (Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.)
Originally released December 13, 1993; last updated May 16, 2020; expires May 16, 2023

This article includes discussion of rabies and hydrophobia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Rabies is an acute viral infection of the nervous system that has both encephalitic and paralytic clinical forms. Transmission of the rabies virus usually occurs in saliva from the bite of a rabid animal. Although rabies is an ancient disease, human rabies continues to be a problem in developing countries, particularly in Asia and Africa. In this article, the author reports that bat rabies virus variants cause most cases of human rabies in the United States, and there is often no history of a bat bite or even contact with bats. Worldwide, dogs are the most important vector. Although rabies can be prevented after an exposure with wound cleansing and the administration of the rabies vaccine and of rabies immune globulin, there is no established effective therapy once rabies develops; the disease is almost always fatal. In developed countries, rabies is often not recognized until late in the course of the disease or postmortem because physicians are not familiar with the clinical manifestations.

Key points


• Bats are the vector for most human rabies cases in North America whereas dogs are the most important vector worldwide.


• Rabies can be effectively prevented after a recognized exposure, but the disease almost invariably is fatal once clinical disease develops.


• Rabies should usually be suspected from the clinical features even if there is no history of an animal exposure.


• Laboratory tests may confirm a diagnosis of rabies, but negative tests do not exclude rabies, and the tests may need to be repeated.


• There is no effective therapy for rabies; more research is needed to gain a better understanding of the mechanisms involved in the disease and for the development of novel therapies.

Historical note and terminology

Rabies has been present since antiquity, and perhaps the earliest reference was in the pre-Mosaic Eshnunna Code of Mesopotamia in about 2300 BC (Rosner 1974). The works of Hippocrates, Aristotle, and Celsus made reference to rabies in humans and animals (Fleming 1872; Baer 2007; Jackson 2013). Ancient Chinese writings also indicate that rabid dogs were recognized centuries before the birth of Christ (Wilkinson 1988). Dog rabies was a serious problem in the Old World during the 19th century, and it was also present in colonial North America (Smithcors 1958). In the early 19th century, Zinke demonstrated experimentally that the infective agent causing rabies was transmitted in saliva by painting saliva from a rabid dog into incisions in healthy animals (Zinke 1804). Louis Pasteur developed the first rabies vaccine, and Joseph Meister, a boy who had been bitten by a rabid dog, was the first patient immunized against rabies in 1885. Rabies remains a serious public health problem in developing countries (World Health Organization 2018).

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