The Democratic candidate, who is seeking to be elected America's first female president on November 8, launched a blistering fightback after the Federal Bureau of Investigation revived its probe, citing new evidence.
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"We are 11 days out from, perhaps, the most important national election of our lifetime," Clinton told reporters, complaining that the FBI announcement posed more questions than answers.
"The American people deserve to get the full and complete facts immediately," she said. "We don't know the facts, which is why we are calling on the FBI to release all the information that it has."
But her defiant words came after Republican rival Donald Trump had seized on the news, declaring Clinton unfit for office as a jubilant crowd of supporters in New Hampshire chanted: "Lock her up!"
Concern that the renewed probe would damage Clinton's seemingly unstoppable momentum rocked the markets, with US stocks, the dollar and oil prices tumbling lower on the prospect of a close vote.
FBI Director James Comey dropped his bombshell in a letter to congressional committees investigating allegations that Clinton had put US secrets at risk during her time at the State Department.
In July, Comey told lawmakers the FBI had not found any criminal wrongdoing in Clinton's unusual decision to use a private server instead of a government email account while serving as secretary of state.
But on Friday he wrote to congressional leaders to reveal that "in connection with an unrelated case, the FBI has learned of the existence of emails that appear to be pertinent to the investigation."
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The FBI will thus take "appropriate investigative steps" to decide whether the new batch of mails contains classified information "as well as to assess their importance to the investigation," Comey wrote.
Clinton's campaign was outraged, and quick to imply that Comey's intervention could be politically-tinged because, in Clinton's words, the letter was only sent to "Republican members of the House."
"We have not been contacted by anyone," she complained. "The American people deserve to get the full and complete facts immediately."
Clinton noted that Comey had said he himself does not know whether the emails are significant or not.
"I'm confident, whatever they are, they will not change the conclusion reached in July," she added.
According to the New York Times, the newly discovered mails emerged after agents seized electronic devices used by Clinton's closest aide, Huma Abedin, and her husband, Anthony Weiner.
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Weiner, a former congressman who resigned in 2011 after he was exposed for sending explicit online messages, is under investigation over allegations he sent sexual messages to a 15-year-old girl.
According to NBC News, the newly discovered emails were sent by Abedin to Clinton from a laptop used by Weiner, who also saw a bid to become mayor of New York founder over similar claims in 2013.
Officials in President Barack Obama's administration said they had learned of Comey's letter and the issues it raises in news reports.
"I don't think anything has surfaced to change the president's opinions and views," White House spokesman Eric Schultz said.
Meanwhile, Trump, trailing in polls both nationally and in the swing states he must win to secure the White House, seized triumphantly on the news.
"We must not let her take her criminal scheme into the Oval Office," the 70-year-old billionaire told cheering crowds at a campaign rally in Manchester, New Hampshire.
"I have great respect for the fact that the FBI and the Department of Justice are now willing to have the courage to right the horrible mistake that they made," he added.
The news took the shine off what should have been a good day for the 69-year-old Clinton, with Obama's Democratic administration announcing stronger than expected economic growth numbers.
While the former first lady holds an overall poll lead, a handful of states -- including Iowa -- could be close-fought.
Both candidates were to be in the battleground of Iowa within hours of each other as they vie to drum up support across the rolling plains of the Midwest.
From Cedar Rapids, Clinton went to the state capital Des Moines to rally voters.
Trump kicked off the day in New Hampshire, jetting to Maine and was to wrap up with an evening rally for 5,000 people in an open-air amphitheater in Cedar Rapids.
While Trump draws the biggest crowds, he is failing to pull in donations to match. Contributions to his campaign slumped in October.
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Both camps filed campaign accounts Thursday for the period leading up to October 19, confirming the Democrat's overpowering lead in the money game.
Trump's campaign was rocked this month by the release of 2005 footage showing him bragging about how his fame allowed him to grope women with impunity, followed by a string of accusations of sexual misconduct -- which he denies.
As he faltered, Trump piled on the defiant rhetoric, claiming the allegations were part of a plot to rig the election, and threatening not to recognize the outcome if he loses.
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