The Poison Belt was the second story, a novella, that Sir Arthur Conan Doyle wrote about Professor Challenger. Written in 1913, roughly a year before the outbreak of World War I, much of it takes place—rather oddly, given that it follows The Lost World, a story set in the jungle—in a room in Challenger's house. This would be the last story written about Challenger until the 1920s, by which time Doyle's spiritualist beliefs had begun to influence his writing.

Challenger sends telegrams asking his three companions from The Lost World - Edward Malone, Lord John Roxton, and Professor Summerlee - to join him at his home outside of London. The cryptic telegrams also instruct each of them to bring a tank of oxygen. When they arrive they are ushered into a sealed room, along with Challenger and his wife. In the course of his research, Challenger has predicted that the Earth is about to come into contact with a belt of poisonous ether, which will, based on its effect on the people of Sumatra earlier in the day, cause the end of humanity. Challenger seals them in the room with the cylinders of oxygen, which he (correctly) believes will counter the effect of the ether. The sealing is not to keep the ether out - it permeates everything - but "to keep the oxygen in".

The five of them wait out the Earth's passage through the band as they watch the world outside die, and machines run amok. (In an interesting display of Victorian values - or, at least, Doyle's take on them - Challenger does not even consider including his servants; they are left outside the room to die, and continue to perform their duties until the ether overtakes them.) Finally, the last of their oxygen cylinders runs dry, and they open a window, ready to face death. To their surprise, they do not die, and they wander through the dead countryside in Challenger's car, eventually making it to London. They encounter only one survivor, who is an elderly, bed-ridden woman prescribed oxygen for her health.

After going to London and back, they make plans for the fate of the world at their hands—when suddenly, people start to wake up again. The effect of the ether turns out to be temporary, and the world wakes up again after a little over a day in a coma, with no knowledge that they have lost any time at all. Eventually Challenger and his companions manage to convince the world what happened - a task made easier by the tremendous amount of death and destruction caused by runaway machines and fires that took place while the world was asleep - and humanity is shocked into placing a higher value on life, and how well we spend what little time we are given.