An envelope addressed to the White House has tentatively tested positive for cyanide after two rounds of analysis.
Additional testing will be necessary to confirm the finding.
The letter was received on Monday at a facility that screens mail for the White House and is located away from the grounds of the executive mansion and its surrounding buildings in the heart of central Washington.
Initial biological testing came back negative, said Secret Service spokesman Robert Hoback.
But additional testing concted yesterday returned a “presumptive positive” for cyanide.
The sample has been taken to another facility for further testing.
The Secret Service, which is responsible for the safety and security of president Barack Obama and his immediate family, said its investigation into the letter was continuing.
Suspicious letters often are sent to some of the country’s leading politicians, including the president.
Some test positive for hazardous substances while others include threats of death or other physical harm.
In 2013, letters sent to Mr Obama, Senator Roger Wicker, and Mississippi judge Sadie Holland tested positive for the poison ricin.
The letters addressed to the president and to the senator were intercepted before delivery, but one letter reached Ms Holland. She was unharmed.
James Dutschke of Tupelo, Mississippi, pleaded guilty in January last year to sending the letters and was sentenced to 25 years in prison.
The Intercept website, which first reported on Monday’s letter to the White House, said it bore the return address of a man who has sent multiple packages to the executive mansion since 1995, including one that was covered in urine and faeces and another that contained miniature bottles of alcohol.