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Jack Sparrow and Barbossa embark on a quest to find the elusive fountain of youth, only to discover that Blackbeard and his daughter are after it too.

At a U.S. Army base in 1941 Hawaii, a private is cruelly punished for not boxing on his unit's team, while his commanding officer's wife and top aide begin a tentative affair.

Two skeletons, a man and a woman killed ten years ago, are discovered. One of them comprise the remains of the former right-hand man of Mondrago, a prominent businessman. McGarrett concludes Mondrago is hiding something and may have killed his late wife and his former business associate. Mondrago is indeed hiding something, but not what it seems. The key to the mystery is Mondrago's daughter, who looks just like her late mother.

Alexander Kline, a brilliant scientist who had worked for the U.S. government, creates the Q strain, a bacteria that can wipe out vast numbers of people in a short time. He quit his U.S. position. To protest research into biological weapons, he will use the Q strain to wipe out Hawaii's population. Five-O catches up to Kline but the scientist has already left a vial with the killer bacteria in a place where it will spread.

A con artist convinces Jeannie that a Hawaiian beach is covered in diamonds.