US federal investigators are probing how vials of smallpox made their way into a storage room at a Food and Drug Administration lab near the US capital, health authorities said.
Smallpox is a highly contagious and sometimes fatal disease that is estimated to have killed some 300 million people in the 20th century alone.
Though there is no treatment for smallpox, it has been eradicated after a worldwide vaccination programme. The last US case was in 1949; the last global case was in 1977 in Somalia.
The vials were labelled "variola", another name for smallpox, and appeared to date from the 1950s, the US Centres for Disease Control and Prevention said.
They were found in an unused portion of a storeroom in an FDA laboratory, located on the National Institutes of Health campus in Maryland.
There was no evidence that the vials had been opened, and "onsite biosafety personnel have not identified any infectious exposure risk to lab workers or the public", the CDC said. The vials have been moved to a high-security lab at the CDC headquarters in Atlanta.
Initial tests came back positive for smallpox, and further testing will be done to determine if it is viable, or able to grow in tissue culture.
"This testing could take up to two weeks. After completion of this testing, the samples will be destroyed," the CDC said.
"If viable smallpox is present, the World Health Organisation will be invited to witness the destruction of these smallpox materials, as has been the precedent for other cases where smallpox samples have been found outside of the two official repositories."
According to international agreements, only two places in the world are authorised to keep samples of smallpox: the CDC in Atlanta and the State Research Centre of Virology and Biotechnology in Novosibirsk, Russia.
Global stockpiles of smallpox still exist so that researchers can study them for vaccines and potential drug treatments in case another outbreak were to occur.
Discovery of the smallpox vials came just weeks after the CDC in Atlanta announced that 80 or more workers may have been accidentally exposed to anthrax.