Early on in the exchanges between the two United States presidential nominees the focus turned to remarks about women made by Donald Trump in a secretly taped video.
In the footage linked to a past television appearance the Republican candidate can be heard talking about making advances on women, including apparently seducing a married woman and inappropriately touching another.
His words have been described as lewd and vulgar, and his actions as sexual assault.
Hillary Clinton says Mr Trump's comments about women and other groups raise questions about his fitness for the presidency.
"It's not only women and it's not only this video that raises questions about his fitness to be our president, because he also targeted immigrants, African Americans, Latinos, people with disabilities, POWs, Muslims and so many others. So this is who Donald Trump is, and the question for us -- the question our country must answer - is that this is not who we are."
Donald Trump's campaign has faced increased criticism since last week's release of the video footage.
During the televised debate at Washington University in the city of St Louis, Mr Trump said he was embarrassed by his comments.
But when asked by moderator Anderson Cooper whether he had groped women, Mr Trump dismissed the recording as locker room banter.
Trump: "I have great respect for women, nobody has more respect for women than I do."
Cooper: "So, for the record you're saying you never did that?
Trump: "I said things that frankly, you hear these things I said, and I was embarrassed by it. But I have tremendous respect for women, and women have respect for me."
Cooper: "Have you ever done those things?"
Trump: "No, I have not."
Mr Trump renewed his attack on Ms Clinton's use of a private email server while she was the Secretary of State, saying that - if he were president - he would have her jailed for it.
A nearly year-long FBI investigation into the matter concluded earlier this year without charges being filed.
But Mr Trump has vowed not to leave the issue alone.
"And I'll tell you what. I didn't think I'd say this, but I'm going to say it, and I hate to say it. But if I win, I am going to instruct my Attorney-General to get a special prosecutor to look into your situation, because there has never been so many lies, so much deception. There has never been anything like it, and we're going to have a special prosecutor."
The two also disagreed on what steps the US should take to tackle the crisis in Syria.
The US government has warned Russia it's killing civilians rather than extremists in the besieged city of Aleppo, which has been under bombardment by Russian and Syrian forces.
Mr Trump says he's no fan of Russia or the Syrian President Bashar Assad, but says the two are fighting against Islamic State militants.
Ms Clinton says - if elected - she would try to rein in Russia's influence.
"We need some leverage with the Russians because they're not going to come to the negotiating table with a diplomatic resolution unless there is some leverage over them. Russia has decided that it's all in in Syria and they've also decided who they want to see become president of the United States too and it's not me. I've stood up to Russia. I've taken on Putin and others."
The topic of Donald Trump's taxes also came up, with Mr Trump blaming Ms Clinton for, as he said, failing to close tax loopholes that have in the past enabled him to minimise his tax bill.
At the end of the debate the two were asked to say something positive about one other.
Ms Clinton spoke about how she admires Mr Trump's children while he said he respected her determination and refusal to give up, even though he disagrees with much of what she is fighting for.
