Republican presidential hopeful in a televised debate in Miami, Marco Rubio has attacked Donald Trump for saying that Islam hates America.
Mr Rubio, who faces a do-or-die contest in Florida on Tuesday, said Islam had a problem with radicalisation but said that many Muslims were proud Americans.
“Presidents can’t just say whatever they want. It has consequences,” he said.
The four Republicans heeded pleas from party leaders to have a civil debate.
Unlike in the last TV event, which was littered with personal insults, this one was more substantive with a focus on policy.
“So far, I cannot believe how civil it’s been up here,” Mr Trump observed at one point.
On the issue of Islam, there was clear distance between Mr Trump and the others. Mr Trump stood by comments he made earlier in the day when he said “Islam hates us, there’s a tremendous hatred, and railed against political correctness.”
But Mr Rubio said: “I’m not interested in being politically correct. I’m interested in being correct.”
All three of Mr Trump’s rivals distanced themselves from Mr Trump’s statement in December that in the fight against terrorist “you have to take out their families”.
“We’ve never targeted innocent civilians and we’re not going to start now” Mr Cruz said.
When Mr Trump was challenged on the legality of targeting civilians, he said that America had to be able to fight on an equal footing.
“We have to obey the laws, but we have to expand those laws”, he said.
On Tuesday five large states will vote for presidential candidate in each party, with Ohio Governor John Kasich and Mr Rubio, a Florida senator, under pressure to win their home states.
Mr Trump picked up a key endorsement of Ben Carson, who last week dropped out of the race before the debate.
The candidates also clashed over President Barack Obama’s historic visit to Cuba next week.
Mr Rubio, whose parents were Cuban immigrants, said he was opposed to restore relations until Cuba improved its human rights record. But Mr Trump said he was not opposed to a US-Cuba deal, but it should be on better terms for the US.
The other Cuban-American candidate on the stage, Mr Cruz, accused Mr Trump of supporting the Obama-Clinton policy on Cuba.
Mr Trump, a billionaire businessman from New York with no political experience, has dominated the news and the state primary contests so far.
On the Democratic side, Vermont Senator Bernie Sanders and former Secretary of State Hillary Clinton are battling for the party’s nomination.
Mrs Clinton is leading Mr Sanders in delegate counts so far, though his campaign has proved more formidable than expected.
Both parties will determine their nominees at conventions in July, then Americans will pick their new president in November.