A recent hiker of the Appalachian Trail said he met only one rattlesnake in his 2,000 mile walk from Maine to Georgia, but that was in Bear Mountain State Park.
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Possibly the most famous river in all of America, the Mississippi River is one of the most snake-infested waterways you'll come to. Thankfully, in most areas, the snake population is skittish enough that you won't see the reptiles.