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San Francisco initially developed as a port city, and its early growth was centered on its waterfront. Almost from the beginning, Market Street has been the central thoroughfare of downtown San Francisco, running from the Ferry Building in the center of the waterfront to the foot of Twin Peaks, a high hill near the city’s center. The Ferry Building was for many years the city's most famous landmark. Built between 1895 and 1903, it features a 235-ft tower designed after a cathedral bell tower in Seville, Spain.

Running inland from the Ferry Building along Market Street and to its north is the Financial District. There modern skyscrapers such as the 48-story Transamerica Pyramid (completed in 1972) and the 52-story Bank of America building (completed in 1969) share the skyline with those from the early 20th century. These skyscrapers house financial institutions, corporate headquarters, and professional offices. West of the Financial District is a shopping district containing major department stores and specialty shops, many of them centered on Union Square. West of Union Square, primarily along Geary Street, is a theater district. Hotels are scattered throughout these last two areas. To the west of these areas is the Tenderloin, a district of inexpensive hotels and low-rent apartments.

There are several distinctive communities north of Union Square. Chinatown has been the center of San Francisco's Chinese community since the 1850s. Its boundaries have expanded significantly since the 1960s, and it is currently one of the largest Chinese communities in the United States. The neighborhoods built on Nob Hill and Russian Hill are generally affluent. Most apartments and condominiums in these neighborhoods are expensive, and because the two hills are very steep, many of them have dramatic views of the bay. Northeast of Russian Hill is North Beach. Once home to many of the city's Italian immigrants and their children, the area is still known for its numerous Italian restaurants. Just east of North Beach is Telegraph Hill, at the top of which stands Coit Memorial Tower. The tower, a memorial to San Francisco’s fire fighters, is 64 m (210 ft) tall and houses several well-known murals.

Directly north of North Beach are Fisherman's Wharf and Pier 39, areas with many seafood restaurants and tourist-oriented businesses. Nearby are Ghirardelli Square and the Cannery, both former industrial buildings that have been converted into fashionable shops and restaurants, and Hyde Street Pier, with its historic ships.

The area south of Market Street was once a region of warehouses, light manufacturing, and working-class residences. Since the 1970s much of the warehousing and manufacturing has left the region, and some parts of it have been incorporated into the Financial District. The South-of-Market, or SOMA, area also includes museums, an entertainment district, and artistic, high-tech, and multimedia enterprises.

Further south is the Mission District, an area that began to develop in the 1870s as a working-class residential area. Retail shopping in the district is centered along Mission Street. Once home to large numbers of Irish immigrants and their families, the Mission District now houses a vibrant Hispanic community drawn largely from Mexico and Central America. To the west of the Mission District, concentrated along Castro Street, is one of the world's largest and best-known gay and lesbian communities. Parts of the Mission and Castro districts include examples of the late-19th-century Victorian houses for which the city is famous. Many of these houses have been renovated or restored since the 1970s.

The areas west of the city center were long undeveloped because San Francisco’s many hills blocked easy access to them. In the relatively flat area just east of Golden Gate Park, however, the Haight-Ashbury section evolved as a middle- and upper-middle-class residential district between the late 19th and early 20th centuries. In the 1960s it became a center for the hippie movement and then descended into drugs and decay. Since the late 1970s much of the area has been renovated, including many of its Victorian houses.

The Sunset District embraces most of the city west of Twin Peaks and south of Golden Gate Park. Most of the district was built as a middle-class residential area with many single-family row houses (houses that have only a very small space between their side walls). A large part of the Sunset District west of 19th Avenue was built up after World War II (1939-1945). Most of the southwestern part of the city, which includes the Lakeshore and Parkside districts and San Francisco State University, was also developed after World War II. North of Golden Gate Park lies the Richmond District, an area much like the Sunset District but with more multiple-unit residences. Since at least the mid-20th century, parts of the Richmond District have been home to a growing Russian community. In addition, an area along Clement Street in the district emerged as a "New Chinatown" in the last part of the 20th century by virtue of its many Chinese-owned businesses.

Between the Richmond District and the Tenderloin lies the Western Addition, built in the late 19th century as a middle- and upper-middle-class residential district. As families began to move to the suburbs after World War I (1914-1918), the large Victorian houses in the area were divided into apartments. During World War II the Western Addition became home to a large African American community. In the 1950s and 1960s large sections of the area were razed for urban redevelopment. More recently, many Victorian houses have been restored and renovated. Two of the city's most exclusive neighborhoods, Pacific Heights and the Marina, are north of the Western Addition. Pacific Heights lies along a range of hills, and the Marina is situated between Pacific Heights and the bay.

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