Boris Johnson has defended his decision to place 55 million people in England into the two highest tiers of Covid restrictions, arguing the country needs "simplicity and clarity".
The PM said measures due to come in when lockdown ends on Wednesday were more "relaxed" but would "drive" Covid down until a vaccine is available.
But a group of Tory MPs is threatening to rebel in a Commons vote on Tuesday.
If Labour backs them, this could threaten the government's majority.
There is concern that the government is adopting a "one-size-fits all" approach, which does not reflect local levels of infection.
From Wednesday, more than 32 million people are due to be living under tier two restrictions, banning indoor meetings between households.
A further 23 million people would be placed under the highest - tier three - restrictions, which further limit contact between people outdoors.
Just over 1% of England's population would enter the lowest - tier one - restrictions, under which the "rule of six" applies both indoors and outdoors.
Conservative MP and former cabinet minister Damian Green, who represents Ashford, in Kent, which is set to go into tier three, told the BBC he would vote against the government unless it provided "new and convincing evidence".
"Instead of having these wide county-based areas, where people are put in tiers, then we should do it on a borough basis," he said.
"In an area like mine, the incidence is less than it is in Liverpool, which has just been released down into tier two. So, as it stands, the current policy, the current allocation of tiers on these wide bases, are just not evidence-based."
Speaking on a visit to Public Health England laboratories, at Porton Down, Wiltshire, Mr Johnson said he understood the "frustration" of those in higher-tier areas, whose own town or village did not have high levels of the disease.
But he added that the government "cannot divide the country up into loads and loads of very complicated sub-divisions" and had to ensure "some simplicity and clarity".
"Unless you beat the problem in the high-incidence area, the low-incidence area, I'm afraid, starts to catch up," Mr Johnson said.
He said "tough tiering" was still more "relaxed by a long way than the current lockdown measures" and it would "drive the disease down... until a vaccine comes on stream, which we hope will be over the next weeks and months".
Asked about mass Covid testing, Mr Johnson said: "The supply [of kits] I don't think is going to be the problem. The issue is going to be getting everybody mobilised to understand the potential advantage of [it]."
Aware of the disquiet on its own backbenches, the government has promised to publish impact assessments of the new restrictions; a key demand from concerned MPs.
There's also a suggestion that areas could move into lower tiers when numbers are reviewed at regular intervals.
But that's unlikely to see off the brewing Tory rebellion.
Some Conservatives have already publicly declared that they won't vote for the new tier system when it's put before the Commons next week.
If enough rebel the government might have to look to the opposition to get this through Parliament.
Sir Keir Starmer is still deciding whether his party will back the plan, although it is likely to have enough support overall.
However, it's not a good look for the government to have to rely on Labour in the face of unrest on its own benches.
The Covid Recovery Group of Conservative MPs, set up to scrutinise the government's response to the pandemic, is threatening a revolt in next Tuesday's vote.
The group's chair, Mark Harper, said evidence provided by the government to justify the tier system was not "compelling". He called for more information on the measures' effects on different sectors of the economy.
He added that on "too many occasions, ministers have made arguments and they've not stacked up".
Deputy chairman Steve Baker called the measures "truly appalling" and said the modelling used by government scientists had been "wrong time and time again".
The group claims to have 70 members, but it is not certain how many of them would be expected to rebel against the government.
Forty-three Conservatives would have to defy the prime minister to defeat the plan, if all opposition MPs also voted against.
Labour leader Sir Keir Starmer is expected to decide early next week whether to support Mr Johnson, after consulting government coronavirus experts.
Shadow health secretary Jonathan Ashworth said Labour was "not against" tougher restrictions or tiers, but would seek "reassurances" on support for the poor and vulnerable.
Under the government's plan, Kent and large parts of the Midlands, north-east and north-west England would go into tier three.
Only Cornwall, the Isles of Scilly and the Isle of Wight would be in tier one.
Mr Johnson said the government's planned "review point" - on 16 December - gave the "prospect of areas being able to move down the tier scale".
But Professor John Edmunds, a member of the government's Scientific Advisory Group for Emergencies (Sage), said he could not imagine "huge changes" to restrictions by then.
He told BBC Radio 4's Today programme that experts were unlikely to "have accumulated much data" in time.
The government has promised to publish an impact assessment before MPs vote on the new rules.
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