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The Turner rebellion was only one of about 200 slave uprisings between 1776 and 1860, but it was one of the bloodiest, and thus struck fear in the hearts of many white southerners. Nat Turner and a handful of slaves spontaneously launched a rebellion in Southampton County, Virginia, in August 1831. They moved from farm to farm, indiscriminately killing whites along the way and picking up additional slaves. By the time the militia put down the insurrection, more than eighty slaves had joined the rebellion, and sixty whites lay dead. While the uprising led some southerners to consider abolition, the reaction in all southern states was to tighten the laws governing slave behavior.

That same year, South Carolina's opposition to the federal tariff led the legislature to declare that the law was null and void in the state, and the state's leaders spoke of using the militia to prevent federal customs agents from collecting the tax. President Andrew Jackson swept aside the states' rights arguments and threatened to use the army to enforce federal laws. In the face of Jackson's determination, the state backed down, but the episode raised fears throughout the South that it was only a matter of time before Congress would begin to tamper with slavery.

Southern anxiety increased in 1833 with the founding of the American Anti-Slavery Society in Philadelphia. Led by the fiery abolitionist William Lloyd Garrison, the Society pledged to end slavery in the United States. The sentiments adopted at the founding meeting established the basic argument of the Society for the next three decades, namely, that slavery was illegal, if not under the Constitution (which Garrison had damned as "a covenant with hell"), then certainly under natural law.