Authorities have obtained records of years-old doping allegations against him and contacted his sponsors, and former teammate Floyd Landis has unleashed new claims about him.
Many of the other big names in American cycling during the past 25 years, including Greg LeMond, also have been drawn in by this inquiry being led, among others, by Jeff Novitzky, who is credited with uncovering baseball's steroid era via the BALCO investigation.
A federal grand jury in Los Angeles will decide where it goes next.
Though federal authorities have not disclosed who they are scrutinizing, dozens of interviews by the AP with people involved in the case reveal a broad investigation that began with cyclists who had records of doping. It then turned toward Armstrong, who has denied using performance-enhancing drugs and has hundreds of clean doping tests as evidence.
Those on Armstrong's side appear willing to fight what has the potential to be the mother of all doping cases. His lawyers contend the investigation is a waste of money. Armstrong said he would be happy to participate as long as it isn't a "witch hunt."
Some people interviewed by the AP believe Armstrong has been on investigators' radar for years. Others say the evidence simply took them on a path that eventually, and without intent, brought them to Armstrong.
PEOPLE FAMILIAR WITH the investigation said Novitzky's investigation began after he was notified about a cache of performance-enhancing drugs that a landlord found in the vacated apartment of Kayle Leogrande, a little-known cyclist with a doping ban who rode for Rock Racing.
Rock Racing, owned by former rider Michael Ball, became the centerpiece of the investigation, according to several people, none of whom wanted their names used because it could jeopardize their access to information. Messages left for Ball and Leogrande were not returned.
After Novitzky got word of Rock Racing, Floyd Landis created a stir in April when he sent e-mails to cycling officials that accused ex-teammate Armstrong, along with his longtime doctor and trainer, and numerous other U.S. cyclists, of running an organized doping program earlier this decade.
That led to subpoenas, including the one handed to LeMond -- a longtime Armstrong detractor -- and reportedly former teammate George Hincapie. Tyler Hamilton, another cyclist tainted by positive doping tests, also is said to have received a subpoena.
Last week, Armstrong sponsors Trek Bicycle Corp. and Nike each said they had been contacted by federal investigators and were cooperating.
Though most of Landis' accusations center on Armstrong's conduct in Europe, federal authorities still have broad areas to explore.
Investigators could consider charging cyclists with a broad range of crimes involving drug violations, fraud, conspiracy and financial wrongdoing. Armstrong's attorneys have said investigators haven't even told them whether the cyclist is a target, nor have they said what they are focusing on.
ARMSTRONG LAWYER TIM HERMAN wrote in a letter last month to the federal prosecutor that many of Landis' claims are beyond the government's jurisdiction to investigate and involve alleged acts that occurred more than five years ago and in other countries. The letter attacked the tactics of Novitzky, a Food and Drug Administration agent whose investigation of the Bay-Area Laboratory Cooperative led to a conviction against Olympic sprinter Marion Jones and perjury charges against baseball slugger Barry Bonds.
Laurie Levenson, a professor at Loyola Law School in Los Angeles and a former federal prosecutor, said prosecutors are likely reviewing documents and trying to determine who they might want to testify before a grand jury.
She said the doping allegations made by Landis against Armstrong and others in recent e-mails won't suffice on their own. Landis is an admitted drug cheat, stripped of his 2006 Tour de France title, who adamantly denied using before deciding to come clean while divulging details about Armstrong.
"His words are only good as the corroboration you have for them," Levenson said. "Other than Landis, who is on the inside and can help as well? If they have another person, it would speed up the process."
It will be hard to find a cyclist who doesn't have a particular slant.
For instance, LeMond has been openly critical of Armstrong and recently said he thought Landis was telling the truth. Any cross-examination of LeMond, though, will refer to his testimony at Landis' drug hearing in 2007, in which LeMond tore into Landis after receiving threatening phone calls from his manager: "I think there's another side of Floyd that the public hasn't seen," LeMond said.
The fate of charges against Armstrong and any others ultimately will rest with the grand jury. The panel operates in secret -- it is made up of between 16 and 23 eligible citizens whose identities are not publicly disclosed. Federal grand juries meet regularly over several months.