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Trigun, a 26-episode Anime series based on a manga, is the story of Vash the Stampede, a.k.a. The Humanoid Typhoon, and the two Bernadelli Insurance agency employees Meryl Stryfe and Milly Thompson who were ordered to follow him and minimize the damage that seems to follow Vash everywhere he goes. Much of that damage is caused by the activities of the bounty hunters who are after the $$60,000,000,000 ($$ = double dollar) reward on Vash's head for the destruction of a city called July (which, amazingly, resulted in no direct loss of life to the city's inhabitants). Vash does not clearly remember the destruction of July, and only wants "love and peace," as he puts it; though he is a gunfighter of near-godlike skill, he uses his weapons only to save lives wherever he can (even the lives of those who try to kill him).

As the series progresses, more is gradually learned about Vash's mysterious history and the history of human civilization on the alien desert planet the series is set on. The series is often humorous in tone, but at the same time it involves very serious character development and especially in later episodes it becomes quite emotionally intense. Vash is occasionally joined by the preacher Nicholas D. Wolfwood, who is almost as good a gunfighter as Vash himself, and later is targetted by a band of mercenaries known as the Gung-Ho Guns for reasons which are mysterious at first.