A man and woman found unconscious in Wiltshire were exposed to Novichok - the same nerve agent that poisoned ex-Russian spy Sergei Skripal, police say.
The couple, believed to be Charlie Rowley, 45, and Dawn Sturgess, 44, fell ill at a house in Amesbury on Saturday and remain in a critical condition.
Police say no-one else has presented with the same symptoms.
There was "nothing in their background" to suggest the pair were targeted, the Met Police said.
Home Secretary Sajid Javid has chaired a meeting of the government's emergency Cobra committee to discuss the developments.
Prime Minister Theresa May said her thoughts were with the victims and the government would provide every support to the community.
"The message from Salisbury is clear - it is very much open for business," she added.
On Saturday, paramedics were called twice to a house in Muggleton Road in Amesbury - first at 11:00 BST after Ms Sturgess collapsed, then later the same day, after Mr Rowley also fell ill.
Wiltshire Police said it was initially thought the two patients had been using heroin or crack cocaine from a contaminated batch of drugs.
In the early hours of Wednesday, police declared a "major incident" after revealing the couple had been exposed to an "unknown substance".
By late that evening, Scotland Yard said Novichok was to blame following analysis at the defence research facility at Porton Down, Wiltshire.
What do we know about the couple's movements?
Partners Charlie Rowley and Dawn Sturgess spent Friday afternoon and evening visiting shops in Salisbury, the city where Sergei Skripal and his daughter Yulia were poisoned.
The following day Ms Sturgess, who is understood to be a mother of three, was taken away on a stretcher by an ambulance crew.
Friend Sam Hobson said she had appeared to have a fit and was "foaming at the mouth".
Shortly after, Mr Rowley started "rocking against the wall", said Mr Hobson.
"His eyes were wide open, glazed and pinpricked, and he was sweating, dribbling and making weird noises."
Mr Hobson said the police and firefighters were in "hazard suits" and "cordoned it all off".
Ms Sturgess' father Stephen, 65, told The Times the family found out she may have been poisoned by a nerve agent from TV news.
"We heard from the hospital on Sunday and we gave them Dawn's GP details but we didn't hear anything from the police.
"We know as much as the next person in the street. We actually called the police station for information."
What is Novichok?
Novichok, a nerve agent developed by the Soviet Union in the 1970s and 1980s, takes effect within minutes, blocking messages from the nerves to the muscles.
This affects breathing, can cause paralysis and lead to the collapse of bodily functions. There are antidotes to help reverse the chemical effects.
It acts quickest when ingested or inhaled and more slowly when contact is made through skin exposure.
Novichok is designed to be persistent - it neither evaporates nor decomposes quickly.
It was used in the UK in March in an attack on former Russian double agent Mr Skripal and Yulia, who were found slumped on a bench in Salisbury - about 10 miles from Amesbury.
The two were critically ill in hospital for weeks but both were discharged in less than three months.
The highest concentration of Novichok was found on the Skripals' front door.
The UK government blamed Russia for the assassination attempt but Russia has denied any involvement and accused the UK of inventing a "fake story".
How did it happen?
The BBC's security correspondent Gordon Corera said the most likely hypothesis was that the Novichok was left over from the attack on the Skripals.
Metropolitan Police Assistant Commissioner Neil Basu said they could not confirm whether the nerve agent came from the same batch but the possibility was "clearly a line of inquiry".
His officers are examining the couple's movements to determine where they were poisoned.
So far no contaminated items have been found and the police say they have no idea what the nerve agent was contained in.
Security minister Ben Wallace said: "The working assumption would be these are victims of the consequences of the previous attack or something else but not that they were directly targeted. That could change."
He called on Russia to fill in the gaps in the Skripal attack and "put this wrong right".
"I'm waiting for the phone call from the Russian state - the offer is there," he told the BBC's Today programme.
Health Secretary Jeremy Hunt said this incident looked like "a very, very unfortunate - and hopefully not tragic - after-effect of that earlier incident".
Chemical weapons expert Richard Guthrie said it was possible that the couple came across the Novichok which poisoned the Skripals after it had been disposed of "in a haphazard way".
However, Vil Mirzayanov, the Russian scientist who first exposed the Novichok programme, cast doubt on the theory, saying Novichok would have decomposed in the four months since the Skripal attack.
He told the BBC this must have been a separate incident because Novichok was unstable, especially in damp conditions.
Are others at risk?
The risk to the general public remains low, says England's chief medical officer Sally Davies.
However, she advises people who had been in the cordoned-off areas to wash their clothes and wipe down personal items.
Residents at John Baker House, the supported housing where Ms Sturgess is believed to have been staying, have been evacuated and told they will have to be rehoused.
The police warned members of the public against picking anything up if they didn't know what it was.
Asked whether the people of Salisbury and Amesbury were at risk, security minister Ben Wallace said the "best intelligence officers in the world" were working on the investigation but until the full picture of the Skripal assassination attempt was known, he couldn't offer complete reassurance.
Sites in Amesbury and Salisbury believed to have been visited by the couple before they fell ill have been cordoned off as a precaution, including a church, park and chemist.
This latest incident is likely to raise fears about the efficacy of a multimillion pound clean-up to decontaminate nine locations across Salisbury after the Skripal poisoning.
What's been the reaction in Russia?
It's "very alarming news", said Dmitry Peskov, a spokesman for President Putin.
"It causes great concern as there have already been numerous such incidents in Great Britain."
He also said he was "unaware of any requests" from the UK in relation to the Amesbury incident.
Russian media: 'Groundhog Day'
By BBC Monitoring
The state media in Russia are deflecting any suggestions of a Russian link to the new poisoning.
Even before it emerged that the Novichok agent was involved, Wednesday night's primetime TV bulletins sarcastically said it was only a matter of time before Moscow gets the blame.
State-run Rossiya 1 suggested it might have been staged by the British government out of spite over the "fabulous" World Cup hosted by Russia.
NTV - owned by state gas giant Gazprom - called it "another dodgy story" from the Salisbury area, this time aimed at deterring fans from coming to Russia.
Again, it added, the British had offered no detailed evidence: "Boris Johnson and British journalists will think up the rest."
Channel One accused the UK of "dragging old skeletons out of the closet" to discredit Moscow ahead of President Vladimir Putin's upcoming summit with Donald Trump.
"Groundhog Day. New Skripals in Salisbury. Really?" said its presenter.