Under-fire Matt Hancock has denied explosive allegations from Dominic Cummings - insisting: "I've been straight with people".
The Health Secretary was battling for his political future after Mr Cummings levelled a series of devastating claims against him over coronavirus failings.
The PM's former aide said Mr Hancock should have been sacked on 15 to 20 occasions in a bombshell evidence session before MPs on Wednesday.
He accused Mr Hancock of lying in meetings and in public, as well as interfering in the rollout of the Test and Trace scheme to meet a "stupid" testing target.
In one of his most serious allegations, Mr Cummings also blamed Mr Hancock for the failure to test patients returning to care homes in the early stages of the pandemic.
Shadow Health Secretary Jonathan Ashworth demanded to know whether Mr Cummings was telling the truth or whether the Prime Minister brought "a liar and a fantasist" into Downing Street.
He said: "Families lost loved ones and have been let down by this Government, this PM and this Health Secretary.
"But the truth matters. These families and the country deserve clear answers from the Health Secretary and the Prime Minister today."
Mr Hancock told MPs: "These allegations that were put yesterday - and repeated by (shadow health secretary Jon Ashworth) - are serious allegations and I welcome the opportunity to come to the House to put formally on the record that these unsubstantiated allegations around honesty are not true.
"I've been straight with people in public and in private throughout."
He added: "Every day since I began working on the response to this pandemic last January, I've got up each morning and asked: 'What must I do to protect life?'"
Mr Hancock also took a veiled swipe at Mr Cummings' criticism over his pursuit of a 100,00 tests a day target last May.
Mr Cummings accused the Health Secretary of interfering with the building of the Test and Trace system to maximise his chances of hitting his target.
"It was criminal, disgraceful behaviour that caused serious harm," Mr Cummings claimed.
But Mr Hancock told MPs: "Setting and meeting ambitious targets is how you get stuff done in government."
Speaking in the Commons, Mr Hancock repeatedly dodged questions on claims that he said people would be tested before they went into care homes when they weren't.
Alba MP Neale Hanvey demanded Mr Hancock resign if these allegations were proven.
Mr Hancock said "so many of these allegations were unsubstantiated" - before trying to shift the blame onto the Scottish Government, which has a devolved responsibility for social care.
Pressed again on care homes by Labour's Barbara Keeley, Mr Hancock said he had answered the question "many times".
