Final answer:
The greatest challenge for settlers and Native Americans in the mid-1800s West was the combination of harsh weather, deadly diseases, particularly smallpox, and difficult terrain. These challenges, coupled with governmental policies toward Native American lands, created a treacherous environment for all involved.
Step-by-step explanation:
The greatest challenge for both American settlers and American Indians in the West in the mid-1800s was the exposure to harsh weather, the threat of deadly diseases, and the danger of crossing difficult terrain. Settlers traveling over trails such as the Oregon Trail encountered severe weather conditions and the persistent danger of diseases like smallpox, to which Native Americans had no immunity, leading to devastating consequences for indigenous populations. Additionally, the terrain of the West posed significant difficulties, featuring arid plains, rugged mountains, and vast distances that had to be traversed.
Despite the romantic notion of the West as an expanse of opportunity, symbolized by the concept of Manifest Destiny, the physical reality of settling this region was fraught with substantial problems and challenges. These arduous conditions were further exacerbated by government policies that sought to confine Native Americans to reservations, disrupting their way of life and contributing to the hardship faced by both groups in this era.