The US House of Representatives has rejected a high-profile trade bill backed by the White House.
Barack Obama made a rare trip to Capitol Hill to drum up support for his "fast track" bill but Democrats in the House voted it down.
The measure would have allowed Mr Obama to negotiate global trade deals Congress could not change, but still approve or reject.
House Minority Leader Nancy Pelosi led the charge against Mr Obama's plea.
Mrs Pelosi called on fellow Democrats to "slow down the fast track to get a better deal for the American people".
The vote specifically was for legislation to renew federal aid for workers who lose jobs because of imports.
Analysis: Anthony Zurcher, BBC News, Washington
The defeat of trade promotion authority legislation in the House of Representatives on Friday marks the beginning of the end of the Obama presidency. With the Republican Party firmly in control of Congress, Barack Obama's best hope for legislative success this year comes from finding common ground with his political opponents.
It's now clear that even on bipartisan issues, like trade, there is no guarantee the president can bring enough Democrats along to ensure success. While all this may sound dramatic, it's part of the inevitable circle of life in US politics.
Every day moves Mr Obama one step closer to the end of his term in office. His influence wanes, and attention turns to the 2016 election, campaigning for which is already well under way. Democratic presidential front-runner Hillary Clinton will likely take note of the president's latest rebuke. If she wants to be her party's standard-bearer, it helps to know which way progressive foot soldiers are marching.
House Democratic Leader Nancy Pelosi did not support Mr Obama's plea for party backing
Mrs Pelosi said she wants to "slow down" Mr Obama's aim to complete the 12-nation Trans-Pacific Partnership agreement, with which this particular bill was intertwined. She said she wants a better deal for America's workers.
A second vote on a portion of the bill having to do with trade negotiating powers passed, but it will not advance without passage of the first part.
Business groups favoured the measure while organised labour groups lobbied against it.
Many Republicans were backing Mr Obama's bill, though some did not want to expand his power.
"I don't think you ever nail anything down around here. It's always moving," Mr Obama said as he left the House floor.
Source BBC
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