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On April 11, 2007, Ivins was put under periodic surveillance and an FBI document stated that "Bruce Edwards Ivins is an extremely sensitive suspect in the 2001 anthrax attacks." In 2008, the FBI requested a review of the scientific methods used in their investigation from the National Academy of Sciences, which released their findings in the 2011 report Review of the Scientific Approaches Used During the FBI's Investigation of the 2001 Anthrax Letters. The FBI responded by pointing out that the review panel asserted that it would not be possible to reach a definite conclusion based on science alone, and said that a combination of factors led the FBI to conclude that Ivins had been the perpetrator.Lawsuits filed by the widow of the first anthrax victim Bob Stevens were settled by the government for .5 million with no admission of liability.The Leahy letter had been misdirected to the State Department mail annex in Sterling, Virginia, because a ZIP code was misread; a postal worker there, David Hose, contracted inhalational anthrax.More potent than the first anthrax letters, the material in the Senate letters was a highly refined dry powder consisting of about one gram of nearly pure spores.The brown granular anthrax mostly caused skin infections, cutaneous anthrax (9 out of 12 cases), although Kathy Nguyen's case of inhalation anthrax occurred at the same time and in the same general area as two cutaneous cases and several other exposures.

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According to the FBI, the ensuing investigation became "one of the largest and most complex in the history of law enforcement." A major focus in the early years of the investigation was a bio-weapons expert named Steven Hatfill, who was eventually exonerated.

The Amerithrax investigation involved many leads which took time to evaluate and resolve.