Official smallpox stocks only remain in two laboratories
Researchers at the UK's Porton Down laboratory estimated the vulnerability of today's population to smallpox and used historical data from Europe and North America to model a modern outbreak.
They concluded the infection would spread rapidly, with each infected individual passing the disease to between six and 12 others.
The infection rate would fall as measures to curb the epidemic were implemented - but before this happened, many would die.
The model produced by the scientists from the Wiltshire research centre is published in the journal Nature.
Terrorist fears
Smallpox, along with anthrax and the botulism toxin, is regarded as one of the most feared potential bioweapons.
Once common throughout the world, the disease was eradicated by 1979 after which routine vaccination gradually ceased.
Official stocks of the virus now remain in only two laboratories, in Atlanta, Georgia, in the United States, and Novosibirsk in Russia.
However, there is increasing concern that the virus might be held secretly and less securely elsewhere, and could be used as a weapon by terrorists or rogue states.
Scientists looked at smallpox outbreaks in the United States and England in the 18th Century.
They also examined a Yugoslavian epidemic which started in Kosovo in 1972, and went unrecognised until the second generation of infection when vaccination and quarantine procedures were initiated.
Risk analysis
The researchers analysed the risk, or R value, associated with different outbreaks which corresponded to the average number of people each person with the disease infected.
Between the 1700s to the 1900s this tended to be in the range of 3.5 to six, but in particular circumstances - such as crowding or hospital-spread infection - could rise to about 10 to 12.
The scientists found a clear relationship between the length of delay before control procedures were put in place and the total number of cases.
They wrote: "Although our estimate for smallpox represents a relatively modest transmission rate by comparison with some other infectious diseases, such as measles and chickenpox, significant epidemics could result, particularly if there were delays in detecting the first cases or in setting up effective public health interventions."