President Jackson faced a number of difficult decisions as his first term progressed. His ambitious agenda began to come under increased scrutiny, and the answers that had seemed so obvious earlier met with the hard political realities of the Congress.

In May 1830, Jackson vetoed his opponent Henry Clay's legislation, the Maysville Road Bill, which would have allowed for the building of a highway in Clay's home state of Kentucky. The issue of "internal improvements" was still a dicey issue in the federal government, and Jackson swore he would not make an exception for one of his main enemies. In fact, while supporters of the Maysville Road decried an end to internal improvements, Jackson allowed some projects to proceed throughout his eight years as President.

On a larger scale, Jackson dealt with the controversial issue of Indian removal. The ever-expanding white population of the United States had pushed about 53,000 Cherokees, Choctaw, Chickasaw, and Creek Indians into what was then the southwestern corner of the United States (modern-day Georgia, Alabama and Mississippi). While the tribes now considered themselves safe under federal treaties, the individual states had other ideas. Georgia, which declared the Cherokee tribe under its jurisdiction, caught an Indian accused of murdering a white settler, and tried, convicted, and sentenced him to hanging. The tribe appealed to the U.S. Supreme Court, saying it was not under the jurisdiction of Georgia state law, and the Supreme Court upheld the appeal–Georgia, unfortunately, had already executed the man.

In a second case, involving missionaries who were charged with living with the Indians, the Court again ruled in favor of the tribes. However, when Jackson heard of the Court's ruling, he is said to have muttered, "Well, [Chief Justice] John Marshall has made his decision, now let him enforce it!" Largely because of cases such as these, Congress passed the Indian Removal Act in 1830, stating that all lands east of the Mississippi would be given over to the government and exchanged for land west of the river given to the Indians in perpetuity.

The removals were a disaster. Over the course of his term in office, Jackson signed more than ninety treaties with Indian tribes, but the government rarely honored these treaties in reality. Tribes were given little time to gather their belongings and were forced to move westward before any planning could be accomplished. Thousands died. Two tribes, the Fox and Sac, were massacred for crossing back over to the eastern shore of the Mississippi to plant grain. The Blackhawk fought a losing war against federal and state troops. Perhaps most serious of all, though, was the battle for Florida–Jackson's old stomping grounds. The Seminoles refused to leave their land, and federal troops spent years fighting them throughout the dense Everglades in southern Florida. Altogether, the war cost the U.S. more than fifteen million dollars. Still later, tragedy recurred when thousands of Cherokees died on the trip west on the infamous "Trail of Tears" in 1838–1839.

While Jackson did believe in states' rights–as witnessed by his hesitation to interfere in Georgia's dispute with the Cherokees–he also firmly believed in asserting the power of the federal government. This assertion became clear in the dispute that arose South Carolina and the issue of nullification.

Even with John C. Calhoun out of his administration for all intents and purposes, Jackson found that the South Carolinian could still cause trouble. In July 1831, Calhoun delivered a detailed statement of his views on nullification: the Union was a compact, so each state could review the acts of Congress and nullify–within its own borders–those laws and acts it deemed unacceptable. The first true test of the nullification idea came a year later, in January 1832, when Henry Clay announced his new tariff plan, the Tariff of 1832. What had begun as an attempt to even out the flaws of the Tariff of 1828 quickly became a battle between Jackson, who tried to preserve the power of the federal government, and Calhoun, who wanted only to win a form of judicial review for the states. Jackson countered Clay's bill with one he supported, a bill that would provide some relief to the South but upheld the protections for the North and West.

The tariff battle became even more personal when, in the midst of the tariff debate, Calhoun led the fight to block nomination of Martin Van Buren as minister to England. The Senate deadlocked on the nomination and it fell to Calhoun, as Vice President, to cast the tie-breaking vote. Calhoun gleefully voted against Van Buren. The move backfired, however, as Jackson swore he would avenge the loss. For his part, Van Buren gained sympathy support around Washington.

Jackson's tariff bill ultimately prevailed and passed both the House and Senate by a wide margin. South Carolina, however, held out. The state called a special session of the legislature to consider its options. With the Union appearing to be breaking up and civil war seemingly looming on the horizon, Jackson ordered army and navy forces to stand ready in Virginia and Charleston. The South Carolina legislature voted on November 24, 1832, to declare Jackson's tariffs null and void and prohibit their collection within the state–and it warned that any force used in an attempt to change the state's decision would force a vote of secession.

Jackson scrambled to stop the "nullies." He looked to the support of Unionists within South Carolina and moved munitions into North Carolina. In his annual message to Congress he explained that if the tariffs were found to be excessive, they would be reduced and reformed. Then, in a December proclamation, he spoke directly to South Carolina, delivering a message of nationalism and unity, explaining that the Constitution empowered him to enforce the Union's laws and asking whether South Carolina really meant to be treasonous. Finally, Jackson introduced what came to be known as the "Force Bill," which granted the government the authority necessary to enforce tariffs. Jackson knew that support across the nation stood firmly on his side, and, indeed, the combined pressures soon brought South Carolina back in the fold. As the Ordinance of Nullification did not take effect until February 1833, South Carolina offered a chance to hash out a compromise before then. It elected Calhoun a U.S. Senator, so that he could bargain in Congress for a good compromise, and so that he could resign as Vice President.

The administration welcomed the change of heart, and Jackson threw himself into crafting a new tariff bill. Clay finally introduced a bill that offered graduated reductions in the tariffs over ten years–a reckless move that would severely harm the nation's economy a decade later, but for now stood as the best option. The bill soon passed both houses of Congress. Meanwhile, Calhoun had tried and failed to kill the Force Bill, so Jackson signed both bills into law on March 2, 1833. A week later, South Carolina repealed the nullification ordinance. To celebrate, Jackson set off on a long tour of the country in the spring of 1833, visiting Staten Island and receiving an honorary degree from Harvard University.

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