The Republican candidates for president traded sharp blows over foreign policy and the future of the Supreme Court in an often unruly and chaotic debate.
After Iowa and New Hampshire, the race has now moved to South Carolina before the 20 February primary.
Front-runner Donald Trump repeatedly tangled with Texas Senator Ted Cruz and former Florida Governor Jeb Bush in a series of tense exchanges.
As the candidates shouted down and interrupted each other, CBS moderator John Dickerson warned: "We're in danger of driving this into the dirt."
Mr Trump said he would work with Congress to penalise companies, which move factories and jobs to Mexico.
Mr Trump and Mr Bush clashed over the war in Iraq and President George Bush's role during the 11 September attacks.
Jeb Bush responded robustly to Mr Trump's attacks, a departure for the former governor who originally sought a "joyful" campaign.
"They lied. They said there were weapons of mass destruction. There were none and they knew that there were none."
Saturday night's Republican debate was like a cross between a game of musical chairs and the opening scene of Gangs of New York. The six candidates remaining in the field are jostling for position in the South Carolina primary next Saturday, and they didn't seem to care whom they have to bludgeon or bloody in the process.
Jeb Bush and Donald Trump led off the night by exchanging barbs over President George W Bush's responsibility for the 9/11 attack on the World Trade Center - a pretty astounding topic for a Republican debate.
John Kasich and Mr Bush fought over expanding Medicaid healthcare coverage for the poor. Ted Cruz and Marco Rubio went at each other (yet again) over immigration reform. Mr Bush and Mr Trump joined in, as well. Cruz and Trump also exchanged blows over Trump's past dalliances with liberal positions.
Ben Carson was also on the stage, but he's been reduced to a ghost of front-runners past.
"My name was mentioned twice," he said at one point, trying to get a word in edgewise.
Mr Bush pushed back, defending his brother who will soon join Mr Bush on the campaign trail before the pivotal South Carolina primary.
"I'm sick and tired of Barack Obama blaming my brother for all the problems that he's had and frankly I could care less about the insults Donald Trump gives against me," Mr Bush said.
Justice Scalia's death was addressed early on in the debate with all six candidates saying the next president should choose his replacement.
Mr Cruz said "we are one justice away" from the court reversing conservative legal gains.
Mr Trump said President Obama would probably pick a replacement, but stressed that Republicans in the Senate should block him.
Later, Mr Cruz contended that Mr Trump, who has supported Democrats in the past, would nominate liberal Supreme Court justices if elected president.
"You are the single biggest liar," Mr Trump said to Mr Cruz. "This guy will say anything."
After South Carolina next week, the rest of the states will have their turn over the coming weeks and months.
Each party formally announces their presidential candidate at conventions in July, four months before the presidential election.