British Airways cabin crew have rejected the airline's latest "final" pay offer by 3,419 votes to 1,686.
Almost half the 11,000 affected Unite union members voted on BA's offer of a 2.9% pay rise next year with 3% the year after.
The no vote raises the prospect of possible new strikes, as union leaders meet to decide their next move.
The vote is the latest landmark in a wrangle whose roots stretch back to before Christmas.
The number of votes cast - just over 5,000 - represented less than half of the unionised cabin crew and was well below previous ballots that saw more than 70% of them express their views.
BA cautiously welcomed the result.
A statement from the company said: "We are encouraged by the result of this ballot which shows that 73% of our cabin crew did not reject our offer."
It said the union has lost the moral authority to represent the views of our cabin crew and urged the union to end the dispute.
'Next steps'
There may now be a move towards another strike ballot. The union has taken strike action on 22 days since March in a bitter industrial dispute that has cost BA more than £150m.
A Unite spokesman said: "The union will now meet with cabin crew representatives this afternoon to consider the next steps."
BA shares stood 1.4% lower at 199p shortly after the announcement.
The BA proposal had also included other elements, including a promise not to victimise staff who have taken part in the often-bitter dispute and a partial re-instatement of staff travel benefits.
Unite did not give its members a guiding opinion on the offer, leaving them to make up their own minds.
However, one of its cabin crew branches, Bassa, had broken down the various elements of the proposed settlement into two lists, of "good" and "bad" points.
It had viewed as "good" the actual pay offer, the promise that work at Gatwick airport could be increased, and the promise of non-victimisation of workers caught up in disciplinary cases.
It had also welcomed the pledge to partially reinstate of staff travel, although this has become the most hotly contested element and also makes it on to the "bad" list - because the promise is only for partial restoration of these.
Lost perks
Before the industrial action, staff built up rights to discounted flights which grew with their length of service. BA has withdrawn the long-service element of these for workers who took action, meaning they have lost perks acquired over the years.
Other "bad" points cited by Bassa included the "vastly reduced" terms and conditions for new staff, and what it says is continued dismissal of staff in what it calls a "disproportionate and unfair way".
The airline views the changes to new recruits' conditions as crucial to its future success as it battles against other carriers whose staff are cheaper to employ. It says it must cut costs substantially to return to profit.
In May, BA reported its biggest annual loss since it was privatised in 1987 - £531m ($788m) in the 12 months to March.
The dispute started last year over BA's plans to cut costs by reducing the number of cabin crew on aircraft, but the row intensified after the airline withdrew travel concessions from staff who went on strike.
Relations worsened after BA took disciplinary action against union members as a result of the dispute, including a number of sackings which Unite now says have reached double figures.
Credit: BBC
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