About 80,000 people could die if there were a "widespread outbreak" of an antibiotic-resistant blood infection, according to a government document.
The National Risk Register of Civil Emergencies says such an outbreak could be expected to hit 200,000 people - and two in five of them "might die".
The document also says "high numbers of deaths could also be expected" from other forms of resistant infection.
It warns infection risk could make "much of modern medicine" unsafe.
The Cabinet Office document says the number of infections "complicated" by antimicrobial resistance is expected to "increase markedly over the next 20 years".
"Without effective antibiotics, even minor surgery and routine operations could become high-risk procedures, leading to increased duration of illness and ultimately premature mortality," it says.
It says procedures such as organ transplantation, bowel surgery and some cancer treatments would become unsafe.
The document, published last month, adds: "If a widespread outbreak were to occur, we could expect around 200,000 people to be affected by a bacterial blood infection that could not be treated effectively with existing drugs, and around 80,000 of these people might die."
It says the UK government is "leading work with international partners" to tackle this "global problem".
Prime Minister David Cameron has previously warned that the world could be "cast back into the dark ages of medicine" unless action is taken to tackle the threat of resistance to antibiotics.
England's chief medical officer, Dame Sally Davies, has called the problem a "ticking time bomb".
Antibiotic use in the UK has been rising and the National Institute for Health and Care Excellence recently called for doctors to "question" the work of colleagues who prescribe too many.
The Cabinet Office document also rates other threats to the UK both in terms of their anticipated likelihood and their "relative impact" - with a flu pandemic and "catastrophic terrorist attacks" given the highest impact ratings.
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