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In announcing his opposition to the bill, Mr. Moran said it fails to repeal the Affordable Care Act or address health cares rising costs.

Vice President Mike Pence, Speaker Paul D. Ryan and Senator Mitch McConnell, the majority leader, discuss the next steps.

There are serious problems with Obamacare, and my goal remains what it has been for a long time: to repeal and replace it, he said in a statement.

In his own statement, Mr. Lee said of the bill, In addition to not repealing all of the Obamacare taxes, it doesnt go far enough in lowering premiums for middle-class families; nor does it create enough free space from the most costly Obamacare regulations.

By defecting together, Mr. Moran and Mr. Lee ensured that no one senator would be the definitive no vote.

House Republicans, after their own fits and starts, passed a bill to repeal the Affordable Care Act in May, a difficult vote that was supposed to set the stage for Senate action. But with conservative and moderate Republicans so far apart in the Senate, the gulf proved impossible to bridge. Conservatives wanted the Affordable Care Act eradicated, but moderates worried intensely about the effects that would have on their most vulnerable citizens.

The Senate Democratic leader, Chuck Schumer of New York, responded to the announcement on Monday by urging his Republican colleagues to begin anew and, this time, undertake a bipartisan effort.

This second failure of Trumpcare is proof positive that the core of this bill is unworkable, Mr. Schumer said. Rather than repeating the same failed, partisan process yet again, Republicans should start from scratch and work with Democrats on a bill that lowers premiums, provides long-term stability to the markets and improves our health care system.

A comparison of public meetings on Obamacare and the Republican bills to repeal it.

Roughly 20 million people have gained coverage through the Affordable Care Act. Repealing the law was a top priority for Mr. Trump and Republicans in Congress, who say it has driven up premiums and forced consumers to buy insurance they do not want and cannot afford.

The opposition from Mr. Paul and Ms. Collins to the latest version of the Senate bill was expected, so Mr. McConnell had no margin for error as he unveiled it. But he managed to survive through the weekend and until Monday night without losing another of his members though some expressed misgivings or, at the very least, uncertainty.

Mr. McConnell had wanted to hold a vote this week, but he was forced to abandon that plan after Senator John McCain, Republican of Arizona, had surgery last week to remove a blood clot from above his left eye. That unexpected setback gave the forces that opposed the bill more time to pressure undecided senators.

Already, Mr. McConnell was trying to sell legislation that was being assailed from many directions. On Friday, the health insurance lobby, which had been largely silent during the fight, came off the sidelines to blast as unworkable a key provision allowing the sale of low-cost, stripped-down health plans, saying it would increase premiums and undermine protections for people with pre-existing medical conditions.

Mr. McConnell has now failed twice in recent weeks to roll out a repeal bill and keep his conference together for it. He first wanted to hold a vote in late June, only to reverse course after running into opposition.

House Republicans in competitive districts who supported their version of the bill will now have to explain themselves and Democrats are eager to pounce.

Make no mistake, Paul Ryan cant turn back time and undo the damaging vote he imposed on his conference, said Meredith Kelly, a spokeswoman for the Democratic Congressional Campaign Committee. House Republicans all own a bill that would strip health care from 23 million Americans and raise costs for millions more, and it will haunt them in 2018.

Mr. Lee, one of the most conservative members of the Senate, was part of a group of four conservative senators who came out against the initial version of Mr. McConnells bill after it was unveiled last month. He then championed the proposal to allow insurers to offer cheap, bare-bones plans, which was pushed by another of those opponents, Senator Ted Cruz of Texas. But the language ultimately added was not quite what Mr. Lee had been advocating, a spokesman said last week.

Mr. Moran, a reliable Republican vote and a past chairman of the Senate Republicans campaign arm, had announced his opposition to the bill as drafted after Mr. McConnell scrapped plans to hold a vote in late June. He expressed concerns about how it would affect Kansas, including whether it would limit access to health care in rural communities and effectively penalize states, like his, that did not expand Medicaid under the Affordable Care Act.

The pressure on Mr. Moran at home showed no sign of relenting. The Kansas Hospital Association said last week that the revised Senate bill comes up short, particularly for our most vulnerable patients.

Robert Pear contributed reporting.

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A version of this article appears in print on July 18, 2017, on Page A1 of the New York edition with the headline: 2 More Defections Lead To Collapse of Health Effort.

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Health Care Overhaul Collapses as Two Republican Senators Defect - New York Times