Gordon Brown bears personal responsibility for creating the sort of culture that allowed a senior Downing Street aide to consider smearing senior Tories, David Cameron said today.
The Conservative leader, who was among those targeted by Damian McBride, said only a change of Government would bring an end to such "nonsense".
"What this whole episode demonstrates is the need for change. Not change in the special advisers code but change in the culture at Number 10 Downing Street," he said
"I do not think we will get a change in culture until we get a change in leadership and we won't get a change in leadership until we get a change of government.
"These people have just been in power too long; they have forgotten who they are serving, what they are meant to be doing, how they are meant to behave and we need some change.
"I do not know what Gordon Brown knew and when he knew it but what I do know is that he hired these people, he sets the culture, he is the leader and we need change in order to change the culture and stop this sort of nonsense."
Mr McBride, a close adviser to the Prime Minister for almost a decade, resigned in disgrace after admitting that he sent "juvenile and inappropriate" emails from his Downing Street account to former spin doctor Derek Draper.
In the private emails, the two men discussed setting up an "attack blog" called Red Rag that would spread unfounded gossip about Conservative opponents and their families.
The Prime Minister wrote to all those targeted by the stories, which he accepts were all untrue, expressing his "deep regret" over the affair.
He also promised to tighten the rules for special advisers but failed to offer the sort of personal apology the victims of the planned smear felt they were owed.
Mr Brown denies any previous knowledge of the emails or the website plans but the Tories have asked Cabinet Secretary Sir Gus O'Donnell to launch a full-scale inquiry.
Speaking as he met NHS campaigners in Stafford, Mr Cameron said: "I am standing here in front of a hospital where there was the most appalling set of circumstances and people being treated incredibly badly.
"That is the priority for me, the NHS. That's the priority for the British people.
"But we need to have a Government that we can trust and believe that it spends its time dealing with the NHS and dealing with the economy and not smearing its opponents."
An investigation was required "to get to the bottom of who knew what and when and how widely this went", he said.
Mr Brown was said by his spokesman to have been "furious" about the emails, the furore over which led to a "huge amount of frustration" in Downing Street that it was overshadowing efforts to get the country out of recession.
Cabinet colleagues have publicly rallied to his support, insisting he could not be held personally responsible for the actions of one adviser.
But other senior Labour MPs said the scandal exposed an unhealthy culture of hostile briefings - often against them - and a serious need for the Government to focus on policy.
Blairite former ministers Alan Milburn and Stephen Byers said they had both been victims of Mr McBride's hostile tactics - with Mr Byers admitting that he enjoyed the former spin doctor's demise.
Mr Milburn told the BBC: "It is very, very important in my view that, as a consequence of the events of these last few days, that we end this sort of approach to politics, which demeans politics, is completely out of kilter with the culture of Labour politics - and that we end it once and for all.
"It is morally unacceptable and it has inflicted huge damage on the Labour Party and the Labour Government."
Writing in London's Evening Standard, Mr Byers admitted making "little effort to suppress a smile when I heard about his enforced departure and warned such tactics had to stop.
"If there remain people close to the Prime Minister who are thinking of fighting the forthcoming general election in a personal and dirty way, then they should go, and go now.
"This is the time for Mr Brown to demonstrate that, as a leader, he is focused on developing and implementing policies that will meet the challenges that face us as a country."
Frank Field, another former minister, said the scandal left Labour MPs "staring into the abyss" and exposed the Government's lack of direction.
Rather than debating how to solve the country's problems, "we see the energy at the heart of No 10 going into trying to smear the opposition", he wrote on his blog.
"It is this contrast between how we should be behaving, and what has been exposed, that is the real killer. A necessary government information machine has been corrupted by a spin that seeks not to inform but control and, if needs be, destroy.
"McBride sat on the Prime Minister's political War Cabinet. If this is the war the Prime Minister thinks the country wants, he is in for a very rude awakening."
Sir Gus, the head of the civil service, was considering today how to deal with a formal call from shadow cabinet office minister Francis Maude for a detailed inquiry into the affair.
Mr Maude said he wanted to find out if ministers knew about the Red Rag website and has specifically asked Sir Gus to investigate whether Cabinet Office Minister Tom Watson was aware of the website plans.
At the weekend, the minister denied any knowledge of the emails or any involvement in "discussions to create the Red Rag website".
The Prime Minister's spokesman, pressed repeatedly on whether Mr Watson had been aware of the plans, would say only that he had "nothing to add" to Mr Watson's own statement.
But he said Mr Brown had full confidence in his colleague, who worked close to Mr McBride.
Former deputy prime minister John Prescott is among Labour figures calling for Mr Draper to be removed from his role in LabourList - his attempt to counter the dominance of right-leaning internet sites.
But the party insisted it was powerless to act as the website is an independent operation.