Rebekah Brooks and her racehorse trainer husband were among six suspects arrested today over allegations of cover-ups in the phone-hacking inquiry.
The News International former chief executive and Charlie Brooks - who has been a friend of the Prime Minister since school - are being held on suspicion of conspiracy to pervert the course of justice, sources said.
Mark Hanna, News International's head of security, was also confirmed by the company as one of those arrested in raids in Oxfordshire, London, Hampshire and Hertfordshire.
Mrs Brooks, a former editor of The Sun, was already due to answer bail later this month after being questioned by detectives last summer on suspicion of phone hacking and corruption.
The dawn raid on her home is potentially embarrassing for David Cameron, who was forced to make further admissions earlier this month about the extent of his relationship with Mr and Mrs Brooks.
After it emerged that Scotland Yard lent an ex-police horse, Raisa, to Mrs Brooks, the Prime Minister conceded it had been among his mounts on rides with Mr Brooks - a friend from their Eton schooldays.
Officers from Operation Weeting - the inquiry into voicemail interceptions - said they consulted the Crown Prosecution Service before carrying out their busiest morning of arrests since the operation was launched last year.
Mrs Brooks, 43, is being questioned at an Oxfordshire police station while Mr Brooks is being interviewed at a Buckinghamshire police station. She was previously arrested and questioned by appointment last July, days after resigning as chief executive.
The force said searches were going on at several addresses after a 39-year-old man was arrested in Hampshire, a 46-year-old man was held in west London, a 38-year-old man was arrested in Hertfordshire and a 48-year-old man was detained at a business address in east London. All six are being interviewed at separate police stations.
Asked about the arrest, a Downing Street spokeswoman said: "The Prime Minister is travelling to Washington. It is an operational matter for the police. You wouldn't expect him to comment on it."