The former business secretary Vince Cable said that Prime Minister David Cameron would have to step down if Britain votes to leave the European Union.
He spoke as the first batch of results put Leave in the lead, ripping away the calm created by earlier polls which had pointed to Remain triumphing.
Cable told the BBC: "It does look increasingly as if Leave are ahead, and we should perhaps begin to think about the political and economic implications of that."
He said that the last minute swing towards Leave was due to "people in highly deprived areas of the northeast expressing their frustration".
"David Cameron would have to leave immediately if it is a Leave vote because his "authority is completely gone", he added.
Late last night over 80 Conservative MPs wrote a letter to Cameron urging him to remain Prime Minister irrespective of the referendum result.
It was signed by all members of the Cabinet who voted Leave and was delivered to Downing Street by Tory MP Robert Syms.
The North East of England and Wales have thrown their weight behind Leave, with commentators saying a higher turnout than in the General Election has increased margins.
Scotland and Northern Ireland appear to sided with Remain — but millions of votes are yet to be counted in London as well as the South-East of England.
A YouGov poll released late last night had suggested Remain would win the EU referendum with 52 per cent of the vote. This was backed up by a subsequent Ipsos Mori poll which put Remain on 54 per cent.
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