The defeat is the second consecutive setback for Republican leaders. Hours after narrowly agreeing to begin debate on health care legislation, Republicans voted down the latest version of Majority Leader Mitch McConnell’s Better Care Reconciliation Act, the most expansive replacement measure the Senate has considered. Nine out of 52 Republicans opposed the plan, leaving it far short of the majority it would eventually need to pass. Opposition came from across the GOP conference, including from Paul and Senator Mike Lee on the right, as well as Collins, Murkowski, and Heller closer to the center. Senators Lindsey Graham of South Carolina, Bob Corker of Tennessee, and Tom Cotton of Arkansas all cast surprising “no” votes against the leadership plan.

Yet none of the votes in opposition were as surprising as McCain’s vote in favor of the McConnell bill. In a floor speech just hours earlier, the Arizona senator who returned from a brain-cancer diagnosis for the health-care debate denounced the same bill and vowed he would not “vote for this bill as it stands today.” McCain spokeswoman Julie Tarallo said Wednesday said McCain’s vote “was procedural.”

“It was not a vote in support of, or in opposition to, the substance of the amendment that was pending at the time,” Tarallo said. “In his speech yesterday, Senator McCain said he would not vote for the health care bill in its current form—and he will not.” Later on Wednesday, McCain unveiled three proposed amendments to the GOP replacement plan, two of which would draw out the end of Obamacare’s Medicaid expansion to 10 years—much longer than conservatives want—and raise the program’s growth rate.

It is true the BCRA vote was procedural in nature. Democrats had raised a point of order against the amendment because it contained provisions that had not been scored by the Congressional Budget Office; therefore, it could not be known whether it complied with the Senate’s budget rules requiring legislation to reduce the deficit by a certain amount in order to pass with a simple majority of 51 votes. What the senators were voting on was to waive the point of order, and the motion needed 60 votes to succeed. So while there was no doubt that the amendment would fail, it was clear that senators were taking a proxy vote on McConnell’s proposal, and the breadth of opposition to it among Republicans suggests it would need major changes in order to come back later in the health-care debate.

The repeal-only amendment senators considered on Wednesday fell despite needing just a 51-vote threshold to pass, and the failure of the two measures, though not surprising, leaves a gaping question for the party: What happens next?

The Senate will take potentially dozens more amendment votes over the next two days, many of them coming in an all-night “vote-a-rama” tentatively set for Thursday evening. Many of them will be political in nature, offered by Democrats to throw off Republicans. Others will, like the first two proposals, be subject to procedural challenges. Partisanship held on the first Democratic amendment, a proposal from Senator Joe Donnelly of Indiana that would have sent the bill back to committee with instructions to remove its Medicaid. Both Collins and Murkowski voted with every other Republican to defeat the amendment, in a sign that they would not buck McConnell altogether. The biggest votes likely will come at the end of the process, when McConnell takes stock of where Republicans are and offers a final amendment representing what he thinks 50 of them might be able to agree to.