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Ride died at her home in the San Diego suburb of La Jolla, said Terry McEntee, a spokeswoman for her company, Sally Ride Science. She was a private person and the details of her illness were kept to just a few people, she said.
Ride rode into space on the space shuttle Challenger in 1983 when she was 32. After her flight, more than 42 other American women flew in space, NASA said.
"Sally was a national hero and a powerful role model. She inspired generations of young girls to reach for the stars," President Barack Obama said in a statement.
NASA Administrator Charles Bolden, a former astronaut, said Ride "broke barriers with grace and professionalism — and literally changed the face of America's space program."
"The nation has lost one of its finest leaders, teachers and explorers," he said in a statement.
Ride was a physicist, writer of five science books for children and president of her own company. She had also been a professor of physics at the University of California in San Diego.
Ride, born May 26, 1951, in southern California, earned degrees in physics and English from Stanford University.
She applied to be an astronaut at US space agency NASA in 1977, after seeing an ad in her university's student newspaper. It was the first time the space agency had allowed applications from civilians -- or from women.
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