Herpes B virus (HB, Cercopithecine Herpes Virus 1) is a primate herpesvirus that has been reported to cause lethal infections in humans. To date, about two dozen well-documented cases of human infections with HB have been reported, with mortality of 75%. HB is indigenous to macaque monkeys, and macaques used in biomedical research including both rhesus (M. mulatta) and cynomologus or long-tailed macaques (M. fascicularis) are commonly infected with this agent without showing any visible signs of disease. Following primary infection, macaques may develop oral or genital herpetic lesions much like those caused by herpes simplex virus (HSV) in humans, and the virus subsequently establishes a latent infection in sensory ganglia. Latent HB virus may reactivate in response to stress and be shed in various body fluids. HB transmission to humans usually occurs from direct contact with body fluids such as saliva from infected monkeys. Primary human disease is characterized by vesicular eruptions on the skin or mucous membranes that are indistinguishable from herpetic lesions caused by HSV1 or HSV2. Unlike typical HSV infections that rarely lead to central nervous system involvement, HB causes a rapidly ascending myelitis and encephalitis that almost always leads to death.