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The extinction of large Pleistocene mammals, such as woolly mammoths, saber-toothed cats, and giant ground sloths, has long puzzled scientists. While climate change and human hunting are often cited, a less considered factor is the role of ancient diseases. This essay argues that hyperdisease—a scenario where a pathogen spreads rapidly through populations with no prior immunity—was the primary driver of these extinctions. Three lines of evidence support this claim. First, the timing of extinctions often correlates with the arrival of humans, who may have introduced novel pathogens via domesticated animals or their own bodies. For example, in North America, megafauna disappeared shortly after the Clovis people appeared, suggesting a disease outbreak. Second, the selective nature of the extinctions—many large mammals died out while smaller species survived—is consistent with disease, as pathogens often target specific host species with similar physiological traits. Third, fossil evidence shows that some megafauna populations were in decline before the most severe climate shifts, implying that disease, not climate, initiated their collapse.

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