Senator John McCain has said he cannot support his fellow Republicans' latest effort to repeal Obamacare, dealing it a potentially fatal blow.
The Arizona senator, who is battling brain cancer, said he "cannot in good conscience" vote for the new plan, which President Donald Trump backs.
Mr McCain said it was wrong to pass such far-reaching legislation without input from both main parties.
Republicans need 50 votes in a 100-seat chamber they control 52-48 to succeed.
But Mr McCain's objection could doom conservatives' seven-year campaign to erase Democratic former President Barack Obama's signature legislative achievement.
One other Republican senator - Rand Paul - also opposes their party's latest bill.
At least five others are undecided: Susan Collins, Lisa Murkowski, Dan Sullivan, Rob Portman and Jerry Moran.
US Vice-President Mike Pence said on Thursday the so-called Graham-Cassidy bill was their "last best chance" to repeal Obamacare.
Senate Majority Leader Mitch McConnell was planning to bring the legislation to a vote next week, but it is not clear now if that will go ahead.
Republicans are still reeling from the collapse in July of their efforts to secure Senate passage of previous legislation to repeal Obamacare.
A dramatic late-night 'no' vote from Mr McCain sunk that bill too.