WASHINGTON - Democratic senators pressed ahead Saturday toward a crucial first vote on an ambitious bill to overhaul the U.S. health care system, a test of party unity in the face of solid Republican opposition to President Barack Obama's top domestic priority.

Democratic leaders are optimistic of success, but they need every Democrat and both independents to vote "yes," and two moderates remained uncommitted ahead of the roll call, which is expected around 8 p.m. EST. The vote will determine whether debate can go forward on Majority Leader Harry Reid's 2,074-page health care reform bill.

"There's much we need to do to make sure we have a health care system that works for all people, not just a few," said Sen. Michael Bennet, a Colorado Democrat, as debate got under way in a rare weekend session.

Most everyone would be required to purchase insurance under Reid's legislation to remake the U.S. health care system over the next decade, and billions in new taxes would be levied on insurers and high-income Americans to help extend coverage to 30 million uninsured. Insurance companies would no longer be allowed to deny coverage to people with preexisting medical conditions or drop coverage when someone gets sick.

Democrats said their legislation could make historic and necessary improvements in the U.S. social safety net. The U.S. is the only major developed country that does not provide comprehensive medical coverage for its people, and Obama campaigned on a promise to change that.

The two moderate holdouts are Sens. Blanche Lincoln of Arkansas and Mary Landrieu of Louisiana. A third centrist, Ben Nelson of Nebraska, announced Friday that he'd be supporting his party on the test vote, while cautioning that it didn't mean he'd be with them on the final vote.

"It is not for or against the new Senate health care bill," Nelson said. "It is only to begin debate and an opportunity to make improvements. If you don't like a bill, why block your own opportunity to amend it?"

If that same reasoning holds with Lincoln and Landrieu, Reid will have the 60 votes he needs to prevail in the 100-seat Senate. The 40 Republicans are unanimously opposed.

A defeat Saturday might not definitively end hopes for a health care bill, but it would cast doubt on whether Democrats can cobble together any plan that the party could rally behind. Also, it would push the debate well into 2010, when the electoral politics of midterm congressional elections could undermine prospects for passage.

A Democratic victory, though, hardly guarantees that Obama's plan -- his top domestic priority -- will pass. Moderate Democrats may agree on Saturday to allow debate to continue, but that does not commit them to supporting the final bill.

These Democratic centrists from conservative states are wary of provisions to have a government-run plan compete with private insurers. Efforts to insert stricter language to bar federal funds from being used to cover abortions has also become a divisive issue.

Even if a bill passes the Senate, it must be reconciled with the version narrowly approved by the House of Representatives. If a compromise can be reached, it would then have to be approved by both chambers.

Landrieu has made comments suggesting she'll support the move to debate, but Lincoln, who faces a difficult re-election next year, carefully avoided taking any public position Friday.

Republicans used their weekly radio and Internet address to slam the legislation, calling it a government takeover of health care that would increase taxes and raise medical costs.

"This 2,000-page bill will drive up the cost of health care insurance and medical care, not down," Sen. Mike Crapo of Idaho said in the address. "This is not true health care reform, and it is not what the American people want. This bill will result in higher premiums and higher health care costs for Americans -- period."

The White House issued a statement late Friday praising the Senate measure.

The action in the Senate comes two weeks after the House approved a health overhaul bill of its own on a 220-215 vote. After the vote Saturday night, senators will leave for a Thanksgiving holiday recess. Upon their return, assuming Democrats prevail on the vote, they will launch into weeks or more of unpredictable debate on the health care bill, with numerous amendments expected from both sides of the aisle and more 60-vote hurdles along the way.

Senate leaders hope to pass their bill by the end of the year. If that happens, January would bring work to reconcile the House and Senate versions before a final package could land on Obama's desk to sign.

The bills have many similarities, including the new requirements on insurers and the creation of new purchasing marketplaces called exchanges where self-employed individuals and small businesses could go to shop for and compare coverage plans. One option in the exchanges would be a new government-offered plan, something that's opposed by private insurers and business groups.

Differences include requirements for employers. The House bill would require medium and large businesses to cover their employees, while the Senate bill would not require them to offer coverage but would make them pay a fee if the government ends up subsidizing employees' coverage.

Another difference is in how they're paid for. The Senate bill includes a tax on high-value medical insurance policies that's not part of the House bill, while the House would levy a new income tax on upper-income Americans that's not in the Senate measure. The Senate measure also raises the Medicare payroll tax on income above $200,000 annually for individuals and $250,000 for couples. Both bills rely on more than $400 billion in cuts to Medicare, the government-run program that provides health care coverage to seniors.