The shuttle launched from Florida's Kennedy Space Center
The space shuttle Discovery has blasted off on its mission to the International Space Station (ISS).
The shuttle, on one of the final missions before the programme is shut down at the end of 2010, is hauling equipment and supplies to the station.
The astronauts are due to carry out three spacewalks, to make repairs on the station and retrieve an experiment.
The shuttle, launched from Florida's Kennedy Space Center, includes three female astronauts for the first time.
The shuttles are coming to the end of their lives as useful vehicles, and the BBC's Andy Gallacher in Miami says it is not yet clear what will replace them.
President Barack Obama is due to visit the Space Center soon to outline Nasa's future direction.
For the first time, there will be four female crew in space
Our correspondent says some 6,000 jobs are expected to be lost as the space programme is cut back.
The White House wants to shut down development of the space vehicles intended to replace the shuttle, which would have taken astronauts back to the Moon by 2020.
But the plans have met with a negative reception in the US Congress. Politicians say the replacement strategy has not been defined clearly enough and lacks a timetable.
In a sometimes emotional interview with BBC News, Nasa chief Maj-Gen Charles Bolden admitted he had been insufficiently prepared to go out and explain the president's plan. But he also expressed determination to win over the doubters.
"I would have explained to people on Capitol Hill and to the American public that we are not losing our leadership in human exploration. We are not losing our leadership in space exploration," he said.
Nasa chief's tears over shuttle
Nasa's shuttle mission management team on Saturday gave a unanimous "go" for launch, despite anomalies seen in recent ground tests of shuttle hardware.
Engineers said the anomalies spotted during tests of booster hardware were unlikely to affect launch safety.
Mike Moses, the space shuttle launch integration manager, said: "We're really excited about this mission and the science we'll be able to get on board for the ISS to do what it needs to do and demonstrate its true ability as a national laboratory."
Spacewalkers Rick Mastracchio and Clay Anderson will replace one of the space station's gyroscopes, which has failed, and switch an ammonia tank.
STATION'S 'MOVING VANS'
Three multi-purpose logistics modules (MPLMs) provided by the Italian space agency
Carry equipment, experiments and supplies
Berthed to the space station using shuttle's robotic arm
Ammonia is used to move excess heat from inside the space station to the radiators outside.
The astronauts will also retrieve an experiment that was placed on the exterior of the Japanese laboratory, Kibo.
The shuttle is carrying about 7,700kg of cargo in a pressurised container dubbed the "moving van" by Nasa - otherwise known as a multi-purpose logistics module (MPLM).
The cargo includes a crew sleeping quarters and science racks which will be transferred to the station's laboratories.
Only four shuttle flights remain - including this one - before the fleet is retired later in 2010.
On Sunday, a Soyuz spacecraft carrying Nasa astronaut Tracy Caldwell Dyson and Russian cosmonauts Alexander Skvortsov and Mikhail Kornienko docked successfully with the station.
During their stay on the ISS, the trio will carry out experiments and support two shuttle missions to the space station.
The assembly of the space station is nearly complete
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