Answer:
The issue that created great conflict between the North and the South in the mid-1800s was slavery. At the time, slavery was legal in the South, and many Southern states relied heavily on enslaved labor for their agricultural economy. In contrast, the North had largely abolished slavery by the mid-1800s and had a more industrialized economy.
The conflict between the North and the South over slavery began to escalate in the 1850s, as tensions rose over issues such as the expansion of slavery into new territories and states, the enforcement of the Fugitive Slave Act, and the Supreme Court's Dred Scott decision, which declared that African Americans could not be citizens and had no rights that white people were bound to respect.
The conflict eventually led to the American Civil War, which lasted from 1861 to 1865. The war was fought primarily over the issue of slavery, with the North seeking to preserve the Union and end slavery, and the South seeking to preserve the institution of slavery and maintain its independence. The Union's victory in the Civil War resulted in the abolition of slavery and the reunification of the United States.