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Fifty years after giant pandas arrived in Washington, D.C., the Smithsonian National Zoo has none in its enclosures, with three of the animals departing on a 19-hour flight to China.

"Goodbye, and bon voyage," was the message from a Chinese diplomat given to the three pandas, who had been living in the nation's capital on loan from China, during their departure Wednesday.

Mei Xiang, the female, was seen in a crate provided by shipping partner FedEx leaving the zoo. She was later joined by Tian Tian and their 3-year-old son, Xiao Qi Ji, in their own crates.

"The three family members are all in good health and ready for the flight," the diplomat said. "Welcome back!"

Brandie Smith, the John and Adrienne Mars director of the Smithsonian's National Zoo and Conservation Biology Institute, called the day one of many historic moments.

GIANT PANDAS TO LEAVE THE NATIONAL ZOO IN D.C. FOR CHINA EARLIER THAN EXPECTED

"There are billions of people who have admired, celebrated, loved our giant pandas and have participated in their conservation," Smith said, adding it has been a "hard morning" emotionally.

The zoo's exchange agreement with the Chinese government, originally brokered by President Richard Nixon in 1972, expires Dec. 7. Ongoing negotiations to extend the agreement haven’t produced results, amid speculation from China-watchers that Beijing is gradually pulling its pandas from Western nations due to deteriorating diplomatic relations with the U.S. and other countries.

GIANT PANDAS TO LEAVE SMITHSONIAN'S NATIONAL ZOO IN WASHINGTON, DC, IN DECEMBER

Bamboo for pandas heading back to China

Zoo workers use a forklift to carry out bamboo for the pandas to snack on during the flight down the Asia trail at the Smithsonian's National Zoo. (FOX 5 DC)

The departure from the National Zoo happened about three weeks earlier than planned. The zoo did not disclose why. A giant "Panda Palooza farewell celebearation" took place from Sept. 23 to Oct. 1 to say farewell to "three of the zoo's most popular residents."

The trio got a police escort to Dulles International Airport in Virginia, where they departed for China on a FedEx plane known as the Panda Express.

FedEx Panda Express plane is seen in 2012

The FedEx Panda Express aircraft is seen in 2012 in Paris. (Franck Prevel/Getty Images)

Giant panda Xiao Qi Ji seen in DC's National Zoo

Giant panda Xiao Qi Ji is seen in his enclosure at the Smithsonian National Zoological Park on Oct. 22, 2023, in Washington, D.C. (Matt McClain/The Washington Post via Getty Images)

Giant panda Xiao Qi Ji seen in DC's National Zoo

Giant panda Xiao Qi Ji hangs upside down from a tree in its enclosure at the Smithsonian's National Zoo in Washington, D.C., on Nov. 7, 2023, on the panda's final day of viewing before returning to China. (Jim Watson/AFP via Getty Images)

The bears have been a wildly popular attraction and an unofficial symbol of the nation’s capital for decades. Every birthday and anniversary was an occasion for public celebration and the long-shot birth of Xiao Qi Ji in the midst of the pandemic in August 2020 drove millions of viewers to the zoo’s panda-cam.

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Zoo officials say they remain hopeful they will come to a new agreement with the Chinese government. The San Diego zoo returned its pandas in 2019, and the last bear at the Memphis, Tennessee, zoo went home earlier this year. The departure of the National Zoo’s bears means that the only giant pandas left in America are at the Atlanta Zoo – and that loan agreement expires late next year.

Fox News' Christine Rousselle and The Associated Press contributed to this report.