Three east London schoolgirls have flown to Turkey and there are fears they may cross the Syrian border and join the Islamic State terrorist group.
Shamima Begum, 15, Kadiza Sultana, 16, and an unnamed 15-year-old, pupils at Bethnal Green Academy, flew from Gatwick on Tuesday (local time), during half-term.
Commander Richard Walton, of the Metropolitan Police, said he feared they were "extremely vulnerable".
The trio are friends with a fourth girl who travelled to Syria in December.
At the time the three girls were interviewed as her friends, police said.
Cdr Walton said the teenagers' families were "devastated" but there was a "good chance" the girls were still in Turkey.
He hoped a police appeal, via social media, would persuade them not to enter Syria.
The girls were last seen at their homes on Tuesday morning when they gave their families "plausible reasons" to be out for the day, police said.
They boarded a Turkish Airlines flight, which landed in Turkey on Tuesday evening.
The third girl is not being named at the request of her family.
Shamima is possibly travelling under the name of her 17-year-old sister Aklima Begum, police said.
Cdr Walton said he hoped the trio would "hear our concerns for their safety and have the courage to return now, back to their families who are so worried about them."
He said the force was becoming "increasingly concerned" about a growing trend of young girls showing an interest or intent in joining Islamic State.
"The choice of returning home from Syria is often taken away from those under the control of Islamic State, leaving their families in the UK devastated and with very few options to secure their safe return," he said.
"If we are able to locate these girls whilst they are still in Turkey we have a good possibility of being able to bring them home to their families."
Shamima and the unnamed 15-year-old were reported missing by their families on Tuesday evening, while Kadiza was reported missing on Wednesday morning.
Home Secretary Teresa May said it was important "to look at the whole question of the ideology that is driving these actions".
"We're very clear as a government that we need to look at extremism across the whole spectrum and that's why we're working on an extremism strategy."
Salman Farsi, a spokesman for the East London Mosque, said she thought the girls had been misled.
"I do not know what was promised to them. It is just sad.
"I think the girls need to know they have done nothing wrong. They have been manipulated."