The parents of Madeleine McCann are flying home to Britain after being named as official suspects in the four-year-old's disappearance.
As the jet took off, they issued a statement saying they "played no part in the disappearance of their beloved daughter".
Gerry and Kate McCann said they were leaving with the "full agreement" of the Portuguese police.
The two doctors were comforted by British holidaymakers on the flight from Faro airport in Portugal.
The plane took off at 9.45 am bound for East Midlands Airport.
It is due to land on British soil at 12:20pm, and the McCanns are expected to return straight to their home in Rothley, Leicestershire.
They are returning 129 days after Madeleine vanished from their holiday apartment in the Algarve resort of Praia Da Luz .
Sky News Online's Kate Sullivan, who is on flight 6552 with the family, said they were whisked through the VIP section and allowed on to the jet first.
Passengers offered words of comfort as they filed past them on the plane.
Sullivan said the McCanns sat with their twins Sean and Amelie in the front row of the plane. The second row has been kept empty to give them some privacy.
She said: "There was a huge media scrum at the airport, with reporters from all around the world.
"The plane is full. But one TV broadcaster was offering significant sums of cash to passengers to try and get on the flight."
Sky News presenter Kay Burley, at Faro airport, said it was a very sad day for the family.
She added: "They arrived as a family of five. They are going back as a family of four."
British passengers on the same flight as the McCanns told Sky News how sad it was for them to leave without Madeleine.
Diana Moran, the former Green Goddess on the BBC's Breakfast Time show, said: "Can you imagine being them? Their nightmare is getting worse and worse and worse.
"I'd love to go up to them and give them a hug."
Another passenger, who gave her name as Becky, said: "I think everyone's thinking just how terribly sad it is for them. It's a tragedy."
The McCanns have no bail conditions attached to their arguido, or formal suspect, status and retain their passports.
Sky News Crime Correspondent Martin Brunt said: "It appears a deal has been struck - the authorities are satisfied that Kate and Gerry McCann will return to Portugal if required.
"The fact they are official suspects and haven't been charged suggests the case against them isn't as strong as the police have suggested."
Earlier, Madeleine's aunt said the couple had been worried that a return would make it look like they are running away.
Philomena McCann, who spoke to her brother Gerry after he was questioned by detectives, said: "(Gerry) doesn't want it to look as if they are running away, because that is nonsense."
Police changed the couple's status from witnesses to suspects after questioning them separately at Portimao police station.
Sources close to the family say detectives believe the two doctors may be responsible for the four-year-old's death - a suggestion rubbished by the McCanns' friends and family.
Meanwhile, a friend of the only other official suspect in the investigation, Robert Murat, has said he expected to be formally cleared soon.
McCanns Family Statement
The McCann family spokesperson gave this statement as the couple boarded their flight to the UK.
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The Long Journey Home
VISEU CAPITAL DA BEIRA NO CORAÇÃO DE PORTUGAL CIDADE DE GRÃO VASCO COM A SUA CATEDRAL IMPONENTE NO ALTO DO MONTE
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