Tony Blair is flying to Washington to become the first international leader to meet US President George Bush since his re-election.
The Blair-Bush relationship has angered many MPs
The Iraq war, Middle East peace and global warming look set to be high on the talks agenda.
The prime minister's close relationship with the Republican president has come under fire from some Labour MPs.
Mr Blair has shrugged off such concerns and says Britain cannot achieve its aims in world affairs without US help.
The Middle East peace process was expected to top the talks agenda, even before the death of Palestinian leader Yasser Arafat on Thursday.
"I think the most important thing is to make sure we reinvigorate the peace process because there is misery for Palestinians, there is misery for Israelis
who suffer terrorist activity," Mr Blair told GMTV.
"And in the meantime we have got a situation where it is a huge source of discontent and problems within the world so it is important we deal with it."
Mr Blair believes momentum has been lost, partly because of the US elections.
But speaking from the prime minister's plane, BBC political correspondent James Landale said aides were playing down expectations the trip would yield any detailed proposals.
Earlier, Mr Blair's official spokesman said: "The priority is to restore that momentum - it is important to get a signal of intent."
But background work had continuing so it was not a case of starting with a "blank page", he added.
Mr Bush on Wednesday said he wanted to see Israel and a Palestinian state existing peacefully together and he wanted to play a part in ensuring there was a chance that could happen.
The two leaders will also discuss progress in Iraq as the US-led assault on Falluja continues.
Mr Blair has faced heavy criticism among some MPs over the decision to allow British Black Watch troops to move to central Iraq to free up US forces for the attack.
He insists it was a military, not a political decision and says the Iraqi interim prime minister wanted the Falluja operation to ensure elections go ahead as planned in January.
Anti-war protesters gathered in Parliament Square on Wednesday and are expected to try to continue their demonstration on Remembrance Day.
The US continues to reject the Kyoto climate change deal
Away from Middle East issues, the future of the four British terror suspects still being held at Guantanamo Bay may also be on the agenda in Washington.
The UK says the men should receive a fair trial in the US or be returned to Britain.
The Confederation of British Industry also wants Mr Blair to complain about American trade "protectionism".
And the prime minister is being urged to persuade the US to back the Kyoto agreement on tackling global warming.
In the Commons on Wednesday, Liberal Democrat MP Norman Baker asked whether Mr Blair's concerns had "been contemptuously swept away in this
one-way street of a special relationship?"
Mr Blair said the differences on the issue were well known, and the US Senate had also overwhelmingly rejected the Kyoto deal.
He insisted he was proud of the US-UK relationship.
"None of these issues, not
climate change, not the Palestinian peace process, not the changes we want to
see in the world, will happen without the engagement of the United States of
America," he added.
Conservative foreign affairs spokesman Michael Ancram has accused Mr Blair merely following the US.
"This must be the moment when the British prime minister ensures that Britain's voice is not only heard loud and clear, but is also given good account," he said.
Liberal Democrat foreign affairs spokesman Sir Menzies Campbell said: "The prime minister constantly defines his relationship with the president in terms of Britain's interests.
"The prime minister needs to show that these interests are indeed being served by his unequivocal support for the Bush Administration."