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The most significant sectional strife over slavery in the first half of the 19th century was driven by the expansion of slavery into newly acquired territories and states following the Mexican-American War. The debate over whether these areas would be free or slave states intensified tensions, exemplified by the Missouri Compromise and the Compromise of 1850. Additionally, the publication of influential works like Harriet Beecher Stowe's "Uncle Tom's Cabin" and the rise of abolitionist movements heightened divisions between the North and South, exacerbating the conflict over slavery.

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