"We increased her (painkiller) dosages and did not get any satisfactory response," National Zoo director John Berry told a news conference. "We concluded that there were no options remaining to us ... At first light today Toni left us."

The zoo has lost dozens of large animals since 1998, including an elephant in 2000, two red pandas mistakenly killed by rat poison, a lion, a zebra, a cheetah and a giraffe.

An investigation by the National Research Council found problems with staff training, workplace culture and strategic planning. The former director resigned in 2004.

Elephant curator Tony Barthel said the zoo's 57-year-old elephant Ambika, who is healthy and free of arthritis, provided evidence that the zoo enclosure was not the cause of Toni's health woes. "She has been living in the current conditions at the National Zoo for longer than Toni was alive," he said.

The zoo has also enjoyed successes, most notably the birth in July 2005 after artificial insemination of giant panda Tai Shan, who has attracted crowds of adoring visitors.

The zoo has also bred nine cheetah cubs in the past two years, as well as rare clouded leopards and red pandas. A male elephant, Kandula, was born in 2001 after artificial insemination.

Zoo staff said they coddled Toni on her last night, feeding her treats such as pineapple, watermelon, grapes and sweet potatoes. Three keepers slept with her.

THREE REMAINING ELEPHANTS

The zoo's three remaining elephants: Kandula; his mother, 30-year-old Shanthi, and Ambika, were put together so Ambika, who had lived with Toni, would not be alone.

Toni came to the Smithsonian Institution's National Zoo in 1989 from a small zoo in Pennsylvania. A leg injury suffered there contributed to her pain, veterinarians said.

Critics have said zoo conditions, including small, concrete-floored enclosures, make elephants miserable.

"Elephants are intelligent and free-ranging animals who live in tightly-knit family groups, walk 10 miles (16 km) or more a day, and have home ranges of up to 200 square miles (500 sq km)," In Defense of Animals said in a statement.

"Science tells us what elephants need," Amy Mayers of the group Friends of Toni said as a guard escorted her off zoo grounds. "Zoos are not doing it."

"I disagree with that conclusion," Berry said. He said zoo programs are important in conserving the endangered Asian elephant and making the animals visible to the public.

"Our medical expertise is second to none," he added.

Some US zoos, concerned over odd behavior and arthritis, have closed or changed their elephant exhibits. In September zookeepers in Anchorage, Alaska, said they were installing a treadmill for their one elephant.

Berry said the National Zoo was rethinking its approach. It is building a larger exhibit for some of its animals and had recently added some soft sand to Toni's enclosure.