Armstrong, 41, admitted for the first time that his decade-long dominance of cycling and seven wins in the Tour de France were owed, in part, to performance-enhancing drugs and oxygen-boosting blood transfusions. He told Winfrey that he was taking the opportunity to confess to everything he had done wrong, including angrily denying reports for years claiming that he had doped.
Investigators familiar with Armstrong's case, however, said today that Armstrong didn't completely come clean. They say he blatantly lied about when he stopped doping, saying the last time he used the drugs and transfusions was the 2005 race.
"That's the only thing in this whole report that upset me," Armstrong said during the interview. "The accusation and alleged proof that they said I doped [in 2009] is not true. The last time I crossed the line, that line was 2005."
"You did not do a blood transfusion in 2009?" Winfrey asked.
"No, 2009 and 2010 absolutely not," Armstrong said.
Investigators familiar with the case disagree. They said today that Armstrong's blood values at the 2009 race showed clear blood manipulation consistent with two transfusions. Armstrong's red blood cell count suddenly went up at these points, even though the number of baby red blood cells did not.
Investigators said this was proof that he received a transfusion of mature red blood cells.
If Armstrong lied about the 2009 race, it could be to protect himself criminally, investigators said.
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Federal authorities looking to prosecute criminal cases will look back at the "last overt act" in which the crime was committed, they explained. If Armstrong doped in 2005 but not 2009, the statute of limitations may have expired on potential criminal activity.
The sources noted that there is no evidence right now that a criminal investigation will be reopened. Armstrong is facing at least three civil suits.
The second half of Armstrong's interview is set to air tonight.
Shock and disenchantment were among the reactions from people most familiar with the famed cyclist's history after his on-air confession Thursday night.
"I could not believe that Lance apologized," Betsy Andreu, the wife of Armstrong's former teammate and close friend Frankie Andreu, said today on ABC's "Good Morning America".
"Lance doesn't say, 'I'm sorry.' Lance isn't used to telling the truth and so I think in the days to come, in the months to come, I'm hoping that we'll see the contrition. Actions speak louder than words so if the words aren't empty ...," Andreu said.
ABC News consultant and USA Today columnist Christine Brennan called Armstrong's admitting that he used performance-enhancing drugs "a major miscalculation."
"This is like Bernie Madoff coming back after three months or Richard Nixon coming back after three months. No one wants to hear from those people so soon," Brennan told George Stephanopoulos on "Good Morning America."
"It was a lose-lose going in. I think he did more harm than good to his reputation, and he just looked cold-blooded, and cutthroat, and ruthless," Brennan said.
Minutes after Armstrong's confession aired on Oprah Winfrey's OWN network, the Livestrong Foundation -- the Austin-Texas-based cancer charity that he founded -- released a statement expressing disappointment in their former leader.
"We at the LIVESTRONG Foundation are disappointed by the news that Lance Armstrong misled people during and after his cycling career, including us," the statement read. "Earlier this week, Lance apologized to our staff and we accepted his apology in order to move on and chart a strong, independent course.
"Our success has never been based on one person -- it's based on the patients and survivors we serve every day, who approach a cancer diagnosis with hope, courage and perseverance."
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Travis Tygart, head of the U.S. Anti-Doping Agency, said in a statement, "Tonight, Lance Armstrong finally acknowledged that his cycling career was built on a powerful combination of doping and deceit. His admission that he doped throughout his career is a small step in the right direction. But if he is sincere in his desire to correct his past mistakes, he will testify under oath about the full extent of his doping activities."
The agency issued an October report in which 11 former Armstrong teammates described the system under which they and Armstrong received drugs with, they say, the knowledge of their coaches and help of team physicians. As a result of the organization's findings, Armstrong was stripped of his seven Tour de France titles. Soon, longtime sponsors including Nike began to abandon him, too.
John Fahey, president of the World Anti-Doping Agency said, "He was wrong, he cheated and there was no excuse for what he did. If he was looking for redemption, he didn't succeed in getting that."
Such a reaction\ to the highly anticipated interview was only the tip of the iceberg as pundits, those close to Armstrong and even everyday people took to Twitter and other social media outlets to share their thoughts on what Armstrong said was "one big lie that I repeated a lot of times."
Cyclist and former Armstrong teammate Jonathan Vaughters tweeted, "A good first step. I need to sleep."
David Walsh, author of the Lance Armstrong book, "Seven Deadly Sins," tweeted, "First reaction is Oprah began the interview brilliantly with her series of 'yes or no' questions. It felt good to hear him admit to doping."
The reaction included Brennan's USA Today column headlined, "If Possible, Armstrong Less Likeable After Oprah."
"He was even more unlikable than one might have imagined. He was smug. He was curt. He was cold and unfeeling," Brennan wrote.
But more legal troubles could be on the horizon for the former Tour de France winner after this tell-all interview.
"He's opening himself up to an enormous amount of possible civil litigation here that could lose him millions of dollars," ABC News legal analyst Dan Abrams said.
Additional reporting contributed by Alexis Shaw, Katie Kindelan, and Colleen Curry.