The jihadi group could use a weaponised form of the black death to target Britons by spraying the disease – which still thrives in some parts of the globe – over a major city.
As the terror cult loses ground in Syria and is pushed out of the Iraqi city of Mosul, anti-ISIS forces and security experts fear the group could resort to desperate measures.
And documents captured from the University of Mosul from the fall of the city detail jihadi experimentation of chemical weapons on human beings, backing up these fears.
Researchers from the World Health Organisation (WHO) estimate a 50kg cloud of the infectious disease released over a city the size of London could infect up to 300,000 people.
The 1665 Great Plague of London left 100,000 people dead – 20 per cent of the city’s population at the time.
Experts on plague fear ISIS could take after historic societies’ use of disease as a chemical weapon.
Stat News writer Eric Boodman said: “After all, the bacteria were being used as weapons long before anyone even knew to call them bacteria.
“Plague-infected corpses were catapulted over walls. Venetians plotted to distill deadly liquid from swollen lymph nodes.
“Japanese planes sprinkled a rainfall of infected fleas. If those with nefarious motives and technical expertise wanted to weaponise the bacteria today, they could.”
The plague, which ravaged Europe in the middle ages, is at its most deadly when contracted within a week.
Symptoms of the horrific disease include fever, vomiting, blisters and painful blood-filled swellings on the neck, armpits and groin.
Both the US and the former Soviet Union experimented with an aerosol version the deadly bacteria during the Cold War.
Rumours and recent attacks have suggested ISIS may have access to chemical weapons – but this has not been confirmed by authorities.
The stark warning comes as international crime-fighting agency Interpol warns a host of trained suicide bombers could be on their way to Europe to wreak havoc.