WASHINGTON – Buoyed by President Bush, supporters of immigration legislation established command in the Senate yesterday, brushing aside potentially crippling challenges to a bill that blends tougher border enforcement with a path to citizenship for millions in the America illegally.

“It was a good way to start,” said Senator Salazar, a Democrat of Colorado, as a shifting bipartisan coalition held firm against attacks from the left and the right.

On a vote of 55-40 that crossed party lines, the Senate rejected an appeal from Senator Isakson, a Republican of Georgia, to require the border be secured before other immigration law changes could take place.

Anything less would mean “a wink and a nod one more time to those who would come here” unlawfully, said the Georgia Republican. The bill’s supporters said he had it backward. “We have to have a comprehensive approach if we’re going to gain control of the borders,” said Senator Kennedy, a Democrat of Massachusetts, echoing Mr. Bush’s remarks of the night before.

Hours later, Senator Dorgan, a Democrat of North Dakota, made an unsuccessful effort to exclude foreigners and recent illegal immigrants from a new guest worker program that could provide jobs for millions over the next decade. “This bill is going to allow illegal workers to come in stamped as legal,” he said, but the vote was 69-28 to scuttle his amendment.

The maneuvering took place at the beginning of what Senate leaders predicted would be a lengthy debate over the most significant changes in immigration law in two decades, an election-year issue that has laid bare deep divisions inside both parties and sparked street demonstrations across the country.

The Senate bill provides additional funds for border security, the guest worker program, an eventual opportunity at citizenship for most of the 12 million illegal immigrants in the country and a tougher program of enforcement to prevent the hiring of illegal workers. Senate passage appears likely by Memorial Day.

Republicans and Democrats alike heralded Mr. Bush’s Monday night Oval Office prime time speech as a turning point, at least as far as the Senate was concerned. The president announced plans to deploy as many as 6,000 National Guard troops in states along the Mexican border, and made his first unambiguous endorsement of a plan to allow millions of immigrants an eventual chance at citizenship as part of a comprehensive approach to the issue.

Senator Martinez, a Republican of Florida, Cuban-born and a supporter of the bill, said Mr. Bush had “solidified some votes” among Republicans. He predicted that the legislation’s supporters had the strength needed to defeat all killer amendments.

“The president gets it,” said Senator Durbin, a Democrat of Illinois, although he and other Democrats were quick to raise doubts about the commitment of numerous congressional Republicans to the approach Bush outlined.

There was ample room for doubt, as Democrats fretted that any Senate-passed bill would be changed beyond all recognition in later negotiations with House Republicans who favor a border security-only approach.

“Thinly veiled attempts to promote amnesty cannot be tolerated,’ said Rep. Tom Price of Georgia, voicing the sentiment that prevails among many House Republicans.”While America is a nation of immigrants, we are also a nation of laws, and rewarding those who break our laws not only dishonors the hard work of those who came here legally but does nothing to fix our current situation.”

But for now, the focus was on the Senate, where Republican and Democratic critics took to attacking the bill without success.

Mr. Isakson went first, brushing aside claims that in seeking to assure the border was under control, he was asking for the impossible. “Listen, this country put a man on the moon in nine years. This country responded to the terrorist attacks on 9/11 within three weeks. This country can do anything it sets its mind to.”

Senator Cornyn, a Republican of Texas, one of the most outspoken opponents of the bill, said Mr. Isakson’s proposal was designed to “put the horse in front of the cart, not the cart in front of the horse. Let’s do first things first.”

Democrats led the counter-attack. The party’s leader, Senator Reid of Nevada, called it a “killer amendment.” Mr. Salazar added, “In the past, for the last 20 years when we’ve tried to approach immigration issue by only looking at one issue at a time, we have failed.” Like many other Democrats during the day, he referred favorably to Mr. Bush’s speech, and said a “comprehensive approach was needed.”

Mr. Mr. Isakson’s proposal drew the support of 36 Democrats and 18 Republicans as well as one independent. Opposed were 33 Republicans and seven Democrats. The entire senior GOP leadership voted in favor of the proposal, including the majority leader, Senator Frist of Tennessee, and Senator Dole of North Carolina, who heads the GOP campaign committee.

“The president needs to talk to his own leaders here if he wants comprehensive immigration reform,” jabbed Mr. Reid. “We’ve got a lot of tough votes coming up.”