The Federal Bureau of Investigation (FBI) says initial tests on a letter addressed to U.S. President Barrack Obama indicate the presence of ricin, a potentially fatal poison.
The FBI said additional tests would be carried out over the next 24 to 48 hours to confirm the presence of ricin.
The letter was intercepted on April 16, the same day authorities intercepted a letter sent to Senator Roger Wicker of Mississippi that preliminary tests showed contained ricin.
The FBI said there was "no indication of a connection" between the suspicious letters and the deadly Boston Marathon bombings.
Both the letter addressed to President Obama and to Senator Wicker were intercepted at off-site mail-screening facilities. All congressional mail has been tested since letters laced with anthrax were sent to two senators in 2001.
The FBI said both letters were postmarked Memphis, Tennessee, and dated April 8.
As word of the suspicious letter to Obama broke, parts of two Senate office buildings at the U.S. Capitol were briefly cordoned off amid reports of suspicious packages.
Senator Carl Levin in a statement on April 17 said the authorities were investigating a "suspicious-looking letter" found at his regional office in Michigan.
Meanwhile, U.S. media reports said investigators probing the April 15 bombings in Boston believe they have identified a suspect from security video taken before the blast.
The reports by CNN and "The Boston Globe," both citing an unnamed source, could not immediately be confirmed.
Three people were killed and more than 180 were injured when two bombs went off at the Boston Marathon on April 15.
White House spokesman Jay Carney said President Obama will bring a message of "resolve" when he visits Boston on April 18.
Obama is to travel to Boston for an interfaith service to remember the victims.
With reporting by CNN, AFP, and AP