Monkeypox is a rare zoonotic viral disease similar to smallpox that occurs primarily in the rain forest countries of central and west Africa. The disease was discovered in laboratory monkeys in 1958. The virus has been isolated from an African tree squirrel, which may be the natural host. Laboratory studies showed that monkeypox also could infect mice, rats, and rabbits. In 1970, monkeypox was reported in humans for the first time, and produces a vesicular and pustular rash similar to that of smallpox. The incubation period from exposure to fever onset is about 12 days, and the typical illness with fever, headache, muscle ache and rash lasts from 2-4 weeks. Other related viruses that cause infections in humans include variola (smallpox), vaccinia (used for smallpox vaccine), and cowpox viruses. Until the current outbreak, however, monkeypox had not previously been recognized in the United States.

There is not enough information to determine with certainty how monkeypox arrived in the United States. One hypothesis is that prairie dogs purchased as pets contracted the virus from infected Gambian giant rats, which were housed in the same animal-holding facility or pet shop as the prairie dogs. The Gambian giant rats were likely imported into the United States from Africa. Studies have shown that Gambian rats and other rodents in Africa have evidence of monkeypox virus infection.

The Centers for Disease Control and Prevention (CDC) has been working closely with state and local health department and others to investigate United States cases of monkeypox virus infections among humans who had direct or close contact with ill prairie dogs that were recently purchased as pets, a Gambian giant rat purchased as an exotic pet, and a rabbit that was housed in a veterinary clinic with an ill prairie dog. The illness has occurred within 7-21 days of exposure to infected animals. As of June 2003, at least six persons with probable monkeypox infection have been reported to be veterinarians or staff at veterinary hospitals. A total of 33 persons with suspected monkeypox have been reported in Wisconsin (18), Illinois (10), and Indiana (5). Monkeypox had been confirmed by laboratory tests in four persons; and seven of the people with suspected monkeypox had been hospitalized for their illness. The possibility of human-to-human transmission in some cases cannot be excluded at this time.