Shaken by the talk of corruption among the friends he had appointed to office, Warren and Florence Harding began a tour on June 20, 1923 of the West and Alaska. He hoped to get out and meet people, to shake hands and explain his policies. Although suffering from high blood pressure and an enlarged heart, he seemed to enjoy himself—especially in Alaska. On his return journey, he became ill with what was then attributed to a touch of ptomaine (food) poisoning. The presidential train rushed to San Francisco, where his condition worsened. On August 2, he most likely suffered a heart attack in the evening, while his wife was reading to him. He died quietly and instantaneously.

Word quickly spread that Mrs. Harding, the last person to be with him that evening, had poisoned him to prevent him from being brought up on charges of corruption that soon engulfed his administration. A sensationalist book published in 1930 detailed the allegations against her. Her refusal to allow an autopsy of the President only fed the rumors. Harding left the bulk of his estate, valued at $850,000, to his wife.