Ministers are gearing up to impose a new contract on thousands of junior doctors across England.
Sources in Government told the BBC an announcement is expected in the next few days.
It comes after the junior doctors and medical students rejected a contract brokered in May, with 58% voting against the deal while 42% voted in favour.
Some 68% of those eligible turned out to vote - around 37,000 junior doctors and medical students.
The move will come as a blow to the British Medical Association (BMA), whose junior doctor lead had urged doctors to accept the deal as the best settlement they may get.
Dr Johann Malawana, chairman of the junior doctors' committee, resigned from his post as the results were announced.
The Government had threatened to impose the contract on several occasions before a settlement was reached with the BMA in May.
Doctors have already staged six strikes over the issue. A spokeswoman for the BMA said there were no plans for future strikes.
A spokesman for the BMA said it would not be commenting this evening on the news that a contract may be imposed.
Health Secretary Jeremy Hunt said earlier he was "extremely disappointed" and the Government would now "consider the outcome".
He said: "It is extremely disappointing that junior doctors have voted against this contract, which was agreed with and endorsed by the leader of the BMA junior doctors' committee and supported by senior NHS leaders."
Mr Hunt highlighted the turnout for the referendum, pointing out that it meant only 40% of those eligible actually voted against the deal.
Dr Malawana said: "The result of the vote is clear, and the Government must respect the informed decision junior doctors have made.
"Any new contract will affect a generation of doctors working for the NHS in England, so it is vital that it has the confidence of the profession."
In a letter, he said he believed continuing in his job "would be dishonourable and untenable".
After forcing the Government "back to the negotiation table twice, I was hopeful that the resulting contract would be acceptable to our amazing membership," he said.
"However, I believe the fundamental breakdown in trust caused by the Government's actions over the last five years has resulted in a situation where no solution is possible, particularly when a Government is so keen to declare victory over frontline staff."
He said the NHS was lurching "headlong into a wider crisis" caused by the Government.
The BMA held more than 130 roadshows across England to show doctors and medical students details of the new contract.
Under the proposed deal, Saturdays and Sundays would attract premium pay if doctors - the vast majority of whom are expected to - work seven or more weekends in a year.
Doctors would receive a percentage of their annual salary for working these weekends - ranging from 3% for working one weekend in seven to up to 10% if they work one weekend in two.
Any night shift would also result in an enhanced pay rate of 37% for all the hours worked.
The deal also set out payment for doctors who are on call, and agreed a basic pay increase of between 10% and 11%.
Asked for David Cameron's response to the vote, the Prime Minister's official spokeswoman said it was disappointing, adding: "We now need to consider the outcome and consider the options, including introducing the contract."
Diane Abbott, shadow health secretary, said: "Today is yet another sorry episode in the saga of the Government's mishandled negotiations with junior doctors. It is disappointing that several months on, we still do not have a contract in place that junior doctors feel able to support.
"We need a Government that can command the support of patients and professionals in the NHS and this Government has shown it can do neither."
New rotas are due to start for 6,000 newly qualified doctors in August, with the rest of the workforce moving on to the contract from then.
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