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.
The lively audience repeatedly jeered and booed the candidates.
As the candidates shouted down and interrupted each other, CBS moderator John Dickerson warned: "We're in danger of driving this into the dirt."
- The death of Supreme Court Justice Antonin Scalia, creating a vacancy on the court, shifted the discussion towards social issues like gay rights and abortion.
- Mr Trump pledged to stop using vulgar terms on the campaign trail.
- Florida Senator Marco Rubio bounced back after stumbling in a previous debate performance.
- Mr Rubio again clashed with Mr Cruz on immigration reform. Mr Rubio said Mr Cruz's shifting position on immigration was just another example of his dishonesty.
- Ohio Governor John Kasich continued to push what he sees as a positive campaign message, decrying the sharp attacks of the night.
- 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.
Mr Bush responded robustly to Mr Trump's attacks, a departure for the former governor who originally sought a "joyful" campaign.
"We should have never been in Iraq," Mr Trump said.
"They lied. They said there were weapons of mass destruction. There were none and they knew that there were none."
Mr Bush pushed back, defending his brother, former president George W Bush, 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 most of the 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.
"Delay, delay, delay," Mr Trump said.
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."
The next primary and caucus is in South Carolina next week. Other 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.
- 20 February - South Carolina primary (Republican); Nevada caucus (Democrat)
- 23 February - Nevada caucus (R)
- 27 February - South Carolina primary (D)
- 1 March - 'Super Tuesday' - 15 states or territories decide
- 18-21 July - Republican convention, nominee picked
- 25-28 July - Democratic convention, nominee picked
- 8 November - US presidential elections