Around 80,000 people in England will be offered urgent tests for the South Africa coronavirus variant after cases with no links to travel were found.
Residents aged 16 and over in eight areas across Surrey, London, Kent, Hertfordshire, Southport and Walsall are being asked to take tests, regardless of symptoms.
The health secretary said the UK must come down "hard" on the variant .
Previous cases in the UK were connected to South Africa.
But random checks found 11 cases that could not be linked to international travel.
Matt Hancock told a Downing Street news conference on Monday that there was "currently no evidence" to suggest the South African variant was "any more severe, but we need to come down on it hard, and we will".
The neighbourhoods being targeted for testing are:
- W7, N17 and CR4 in London
- WS2 in Walsall
- ME15 in Maidstone, Kent
- PR9 in Southport
- EN10 in Broxbourne, Hertfordshire
- GU21 in Woking
Appealing to residents of these postcodes, Mr Hancock added: "It is imperative that you stay at home, and that you get a test, even if you don't have symptoms.
"This is so important so that we can break the chains of the transmission of this new variant, and we've got to bring this virus to heel."
Prof Adam Finn, a member of the Joint Committee on Vaccination and Immunisation (JCVI), said a "real effort" should be made to try to "eliminate" the South African variant before it took hold.
Prof Jim McManus, the director of public health for Hertfordshire, said if every single case was detected, it might be "possible" to eradicate the variant within two weeks.
He warned that officials "may find this has spread beyond that, so it may take three weeks or more, but we will give this everything we have got," he told the BBC.
Asked about the effectiveness of vaccines against the South African strain, Dr Susan Hopkins, strategic response director at Public Health England, said: "Three of the vaccines that have been used to date in the trials have shown that they've been effective against the South African variant at a level greater than was set as the minimum standard by the WHO.
"We expect all other vaccines to have a similar level of effectiveness, particularly in reducing hospitalisation and death."
Almost 9.3 million people in the UK have now received a first dose of a coronavirus vaccine, according to the latest government figures.
Meanwhile, a further 18,607 new infections were recorded in the UK as of Monday, as well as another 406 deaths within 28 days of a positive test.
In total, 105 cases of the South African variant have been identified.
The 11 cases are not tied to people who had travelled to South Africa, or to the other known cases, prompting fears they may have caught it in the UK.
And the government has now advised local authorities to begin mass testing in a number of neighbourhoods where these cases have been identified.
In some areas, home testing kits are also being sent to households.
Positive cases will be analysed to see if they are caused by the South African variant.
Hit hard and early
This development sounds alarming - with just a handful of cases prompting a massive effort to get tens of thousands of people tested.
But as always context is needed.
This variant is - like the UK one - more contagious.
But there is no evidence that it causes more serious illness.
And data suggests the vaccines will work against it, although maybe not quite as well as they do against the original one.
So the logic of public health officials is to stop or at least slow the spread.
We are at a crucial point with the vaccine being rolled out quickly and immunity being built up by significant numbers of vulnerable people.
Anything that interferes with that will slow our escape from lockdown and, ultimately, the pandemic as well as increasing risk to the population.
So the aim is to hit it hard and early.
The fact the UK is the world leader in sequencing - the process of analysing positive cases in detail - means officials have been able to identify the early signs of community transmission, giving the country a fighting chance of stamping down hard on this variant.
Dr Susan Hopkins, of Public Health England, urged people to come forward in these areas.
"We are trying to contain this so it does not spread," she said.
Kent County Council said police staff would be among those going door-to-door to offer residents in the ME15 area tests "there and then". In Hertfordshire, residents in the EN10 area will receive a letter offering tests at mobile screening units, to collect at a local library, or through the post, the county council said.
Public Health England has been analysing around 5% to 10% of all positive cases in more detail, allowing it to identify new variants in the community.
In December, the discovery of the new strain prompted a ban on foreign nationals travelling into the UK from South Africa and later from southern African countries.
Under current restrictions, people arriving into England from anywhere outside the UK, Ireland, the Channel Islands or the Isle of Man need to isolate at home for 10 days and provide a negative Covid test result before travel.
A new system of quarantine requiring those arriving from countries under travel bans to isolate in hotels is due to be introduced in the coming weeks.
There are signs the South African variant makes vaccination a little less effective.
Studies are underway into how the vaccines work against the new variants, with some early results suggesting the Pfizer jab protects against them.
Meanwhile, early results from Moderna suggest its vaccine is still effective against the South Africa variant.
But Prime Minister Boris Johnson said vaccines would still give a high degree of immunity nonetheless, adding the vaccines could be adapted to deal with new variants if necessary.
"The fact is we are going to be living with Covid for a while to come in one way or another," Mr Johnson said.
"I don't think it will be as bad as the last 12 months, or anything like, of course.
"But it's very, very important that our vaccines continue to develop and to adapt - and they will."
Meanwhile, Mr Johnson said that, if things go well, he would be "optimistic" about the chances of Britons enjoying a summer holiday this year.
The success of the vaccine rollout and level of Covid cases would be factors taken into consideration, he said.
It came as the NHS announced that a Covid vaccine has been offered to all older residents at eligible care homes in England.
NHS England said more than 10,000 care homes with older residents had been offered jabs, hailed as a "significant milestone".
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