Since author Edgar Allan Poe does not specify the year, location or type of disease in his macabre short story, "The Masque of the Red Death," we can only speculate upon the actual type of disease. Poe uses the word "pestilence" to describe the Red Death, and he seems to have deliberately avoided using the word "plague." One would assume that the pestilence was akin to the Black Death, a plague which devastated Europe during the 14th century. It wiped out nearly half of Europe's population, and it returned intermittently until it was finally eradicated for good in the 19th century.

According to Poe scholars, Poe may have been using the Red Death to illustrate the devastation that tuberculosis was wreaking on Poe's family and friends, including causing the death of his wife, Virginia. Incurable and fatal at that time, tuberculosis would not have caused such a swift end as the Red Death, however. Yet another critic claims that the Red Death was not a disease but Death himself, shrouded in mask and costume and in human form.