Detectives are targeting 12 British potential suspects as they launch a new investigation into the disappearance of Madeleine McCann.
A Metropolitan Police team says they are among 38 "persons of interest" in the case and they are working on the assumption that Madeleine - aged three when she went missing in 2007 - may still be alive.
Officers have completed a two year review of the stalled Portuguese inquiry and say they are moving to an "investigative stage".
They now intend to pursue further information on the dozens of individuals they want to speak to over the suspected abduction of Madeleine from her family's holiday villa in Praia da Luz.
Kate and Gerry McCann said they "warmly welcome" the latest development in the search for their missing daughter.
The Met intends to apply to issue formal requests to Portugal for evidence to be gathered and to allow a team of British officers to be present during the process.
The working relationship between UK and Portuguese police is now said to be "positive and focused" after previous attempts at cooperation faltered amid intense interest in the case.
Detective Chief Inspector Andy Redwood, who is heading up the inquiry, calls this "a critical moment" in the the search for Madeleine.
He said: "We have been in a unique position over the last two years in drawing together three strands - Portuguese, UK and private investigators' material.
"From that vast quantity of material analysed we have identified 38 persons of interest and 12 who are UK nationals, and it is from that position that we are able to move from review to investigation."
DCI Redwood added: "There is no clear, definitive proof that Madeleine McCann is dead.
"On that basis I genuinely believe there is a possibility she is still alive. And so I would like to ask the public to continue to look for her."
Madeleine vanished from her bedroom in the Portuguese resort in May 2007 as her parents dined with friends nearby.
The local police investigation was called off a year later, yielding few clues into her disappearance or whereabouts.
In 2011, the Met launched its review of the case and earlier this year it was reported that around 20 "persons of interest" had been identified.
The Home Office said in June that it was prepared to fund any continuing investigation.
Met detectives have made 16 visits to Portugal and officers have met and shared their findings with key members of both the Policia Judiciaria and the judicial authorities.
A spokesman for the McCanns said: "Kate and Gerry warmly welcome the shift in the Met's emphasis from review to investigation.
"It is clearly a big step forward in establishing what happened and, hopefully, towards bringing whoever is responsible for Madeleine's abduction to justice."