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Spanish explorer Gaspar de Portola first explored the area around the present-day city of Los Angeles in the year 1769. Three short years later, Father Junípero Serra established a Franciscan mission at San Gabriel and, in 1797, a mission at San Fernando. In 1781, Felipe de Neve formally founded the city of Los Angeles, or el Pueblo de Nuestra Señora la Reina de Los Angeles de Porciúncula (the City of Our Lady the Queen of the Angels of Porciúncula), as it was called by the Spanish, and later the Mexicans. Neve was the Spanish governor of California and helped promote the migration of peoples north from Sonora, Mexico. Juan Bautista de Anza greatly aided this migration with the founding in 1774 of an overland trail that ran between northern Mexico and California.

The first peoples to settle in the Los Angeles Basin throughout the latter part of the 18th century were poor farmers and rancheros in search of grazing pastures. By 1784, the first three large ranchos were established in California by Spanish government officials and given to three entrepreneurial families in the business of raising livestock: the Verdugos, Nietos, and Dominguezes. Six years later in 1790, the population of El Pueblo, as it was known throughout the early 19th century, was established at 139.

In 1821, Mexico gained her independence from Spain, but the instability of the infant Mexican government, combined with the distance between Mexico City and California, allowed California to remain quasi-independent, with a distinct identity. As time progressed, more Mexicans began to trickle northward in search of lands, much of which had been confiscated from the Church and dispersed to various ranchero families by the government. Between the years of 1826 and 1831, El Pueblo saw white men for the first time, as men such as Jedediah Strong Smith, James Ohio Pattie, William Wolfskill, and other trappers continued their search for financial gain. In fact, both Smith and Pattie were imprisoned while in El Pueblo, and Pattie was forced by the Mexican mayor, or alcalde, to vaccinate the locals against smallpox in 1826. There are several different sources for this fact, and it is believed that Pattie did indeed vaccinate around two thousand local Mexicans in the Los Angeles area.

By 1835, El Pueblo was designated by the Mexican Congress as Alta California's capital, a decision that embittered the former capital of Monterrey. It was not until 1845, however, that California's last Mexican governor, Pío Pico, moved the capital to Los Angeles. Throughout the following decade, El Pueblo experienced many factional problems that allowed the influx of numerous white settlers in search of land, financial security, and, by the 1840s and 1850s, gold. Mexico and its northern territories encountered its biggest problem starting on August 13, 1846. On this date, Commodore Robert F. Stockton sailed into the waters just west of El Pueblo and established an American military presence in Alta California. Infuriated by such actions, the locals surrounded a military force under the command of Marine Captain Archibald Gillespie. The American detachment was forced to retreat to what is now San Pedro until reinforcements could arrive. The Battle of the Old Woman's Gun ensued, with the Mexicans emerging victorious. Less than five months later, in January 1847, officers Stockton and Stephen W. Kearney retook El Pueblo, and the end of skirmishes in the Mexican-American War was seen in California. On January 13, 1847, the final band of Mexican forces, led by Andres Pico, surrendered to John C. Frémont, and the Cahuenga Capitulation was signed.

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