As a whole, the Didelphidae are no threat or bother to humans. People hunt and eat some species and use their fur for clothing and parts of clothing. The gray short-tailed opossum frequents houses in South America, where it is welcome because it hunts and eats rodents and insects infesting the houses.
Brown four-eyed opossums, gray four-eyed opossums, woolly opossums, and common mouse opossums occasionally raid fruit and corn crops. The southern opossum, and the white-eared opossum sometimes kill poultry.
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