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Mexico won its freedom from Spain in 1821 after an eleven-year struggle. Texas was a semi-independent territory of Mexico at that time. American colonists had been allowed to settle in Texas and own land provided they became Catholic. When Mexico redefined its territories in 1824, Texas lost its independence. It was merged with Coahuila and the capital was moved from San Antonio de Béxar to Saltillo.

Citizens gathered in armed protest and in September 1835 petitioned for separate statehood. Their requests and complaints were submitted in The Declaration of Causes. This document was intended to convince Mexico that the Texans only wanted to uphold the 1824 Mexican Constitution, which guaranteed the rights of Mexican residents. Santa Anna was in power and he sought the removal of all foreigners from Mexico. He sent his best troops, commanded by General Martín Perfecto de Cós, to San Antonio to disarm the Texans.

Under General Cós' command, San Antonio de Béxar was occupied by 1,200 Mexican troops and put under military rule in October 1835. On December 5, 200 Texas volunteers under Ben Milam attacked Cós' troops in San Antonio de Béxar, about 400 yards from the Alamo compound. Cós flew the white flag of surrender from the Alamo on December 9. More than 200 of his men lay dead, and about 200 more were wounded. He signed surrender papers, giving the Texans all of the public property, money, arms and ammunition in San Antonio. The Texans lost 20 men, including Ben Milam.

Cós' surrender brought an immediate response from Santa Anna. He put together an army of 8,000 men, many of them mercenaries from Europe and The United States. Even though it was winter, Santa Anna pushed his army toward Texas. The cold, windy deserts of northern Mexico took a heavy toll as men and animals died by the hundreds and were left behind on the trail. When the big siege guns got stuck in a quagmire, Santa Anna carried on without them.

After the defeated Mexican force of General Cós left San Antonio, Colonel James C. Neill assumed command of the Alamo garrison. He had a total of 80 men, poorly equipped soldiers and volunteers. His command included an artillery company, the Invincibles, under Captain William R. Carey, two infantry companies known as the New Orleans Greys under Captain William Blazeby, and the Béxar Guards commanded by Captain Robert White.

On January 17, 1836, Sam Houston, the commander of the revolutionary troops, sent Colonel Jim Bowie and 25 men to San Antonio to destroy the Alamo fortifications and move east with the artillery. Bowie and Neill agreed that it was impossible to remove the 24 captured cannons without oxen, mules or horses. They did not want to abandon that much firepower. Knowing that General Houston needed time to raise an army to repel Santa Anna, Bowie started reinforcing the Alamo. Neill had to leave because of sickness in his family.

Colonel William Travis arrived in San Antonio on February 2 with a small cavalry, raising the number of Alamo defenders to about 130. Spies had told Travis that Santa Anna had crossed the Rio Grande, but he did not expect an attack before spring. He sent many letters, pleading for supplies and more men. He and Bowie were in competition for command of the defenders before it was decided that Bowie would command the volunteers and Travis the regular army.

On February 9 David Crockett and 14 Tennessee Mounted Volunteers rode into San Antonio. The Mexican army was on the outskirts of town as Travis renewed his pleas for help. In a February 24 letter, he wrote: "To the People of Texas and All Americans in the World.... I shall never surrender or retreat.... Victory or Death!".

The day before, February 23, Santa Anna had recaptured San Antonio. He took possession of the town, set up headquarters on the main plaza, and began the siege. He had some of his men climb to the top of the bell tower of San Fernando Church and unfurl the scarlet flag of "no quarter." Travis and the Texans fired their message to Santa Anna with a blast from the cannon.

Santa Anna ordered his men to bombard the mission with cannons and rifles for 12 days and nights. He wanted to wear out the defenders by giving them no chance to rest or sleep. The noise distracted his own army too and they allowed many couriers to escape from the Alamo. On March 2 the last group of reinforcements arrived. These men were from Gonzales, the only town to answer Travis' pleas to send help. The total number of defenders at the Alamo was between 180 and 190.

At 4 o'clock on the morning of March 6, 1836, Santa Anna positioned his men within 200 yards of the Alamo's walls. As dawn broke, Santa Anna's first attack was driven back, as was the second, by the fire of Travis' artillery. On the third try, one Mexican column attacked a breach in the north wall, another in the chapel area, and the Toluca Battalion started to scale the walls. Out of 800 men in the Toluca Battalion only 130 survived. The fighting was hand to hand with knives, pistols, clubbed rifles, knees and fists. Blood was spilled in the convent, the barracks and in the church interior itself. The battle lasted 90 minutes, and then it was over.

All the Texas defenders died. The Mexican army lost 1,544 men and more than 500 were wounded. Santa Anna dismissed the Alamo as "a small affair". He ordered all the bodies of the Texans to be stacked in three heaps, mixed with fuel, wood and dry branches from the neighboring forest, and set on fire.

Six weeks after the Alamo Santa Anna was defeated at San Jacinto.