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Disease mostly. Also on account of the Aztecs having many Native American enemies.

Disease was probably the number one killer in the New World. Smallpox being the most common. Disease brought entire civilizations down such as the Incas and many Native American tribes. This is mainly due to Native Americans not having any resistance in their bodies to these new diseases brought by the Old World.

When the Aztecs rose to the major power in Mexico, they made quite a few enemies. When the Spaniards came, they used this to their advantage. Also some tribes joined the Spaniards partly because they thought they were gods or due to their "lightning sticks" (muskets).

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