Venice's long decline started in the 15th century, when it first made an unsuccessful attempt to hold Thessalonica against the Ottomans (1423-1430). She also sent ships to help defend Constantinople against the besieging Turks (1453). After the city fell to Sultan Mehmet II he declared war on Venice. The war lasted thirty years and cost Venice much of her eastern Mediterranean possessions. Next, Christopher Columbus discovered the New World. Then Portugal found a sea route to India, destroying Venice's land route monopoly. France, England and Holland followed them. Venice's oared galleys had no advantage when it came to traversing the great oceans. She was left behind in the race for colonies.
The Black Death devastated Venice in 1348 and once again between 1575 and 1577. In three years the plague killed some 50,000 people. In 1630, the plague killed a third of Venice's 150,000 citizens. Venice began to lose its position as a center of international trade during the later part of the Renaissance as Portugal became Europe's principal intermediary in the trade with the East, striking at the very foundation of Venice's great wealth, while France and Spain fought for hegemony over Italy in the Italian Wars, marginalising its political influence. However, the Venetian empire was a major exporter of agricultural products and, until the mid-18th century, a significant manufacturing center.
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