On July 4, 1850, Taylor was known to have consumed copious amounts of ice water, cold milk, green apples, and cherries after attending holiday celebrations and the laying of the cornerstone of the Washington Monument. That same evening, he became severely ill with an unknown digestive ailment. Doctors used popular treatments of the time. Taylor died in the White House at 10:35 p.m. on July 9, five days after becoming ill. Contemporary reports listed the cause of death as "bilious diarrhea, or a bilious cholera".

The remains were exhumed and transported to the Office of the Kentucky Chief Medical Examiner on June 17, 1991. Neutron activation analysis conducted at Oak Ridge National Laboratory revealed no evidence of poisoning, as arsenic levels were too low. The analysis concluded Taylor had contracted "cholera morbus, or acute gastroenteritis", as Washington D.C/ had open sewers, and his food or drink may have been contaminated.

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