The space shuttle Discovery is being prepared for launch from the Kennedy Space Center in Florida.
The seven astronauts are strapped into their flight seats aboard Discovery ready for the scheduled 1549 EDT (1949 GMT) lift-off.
But poor weather could still prevent the flight; conditions around Cape Canaveral remain "dynamic", Nasa said.
Launch preparations continued despite reports of electrically-charged anvil clouds and lightning in Florida.
The astronauts left for the launch pad at noon local time.
Dressed in the distinctive bright orange spacesuits, they waved and gave thumbs up as they boarded the silver-coloured bus that took them from their quarters to launch pad 39B at Kennedy Space Center.
The shuttle's hatch has been closed, sealing the five-man, two-woman crew into the cockpit.
Discovery is going to the International Space Station (ISS) to deliver supplies and equipment and to drop off a new resident crewman, German Thomas Reiter.
He is set for a six-month stay aboard the orbiting platform, becoming the first European Space Agency astronaut to experience an extended tour on the ISS.
Nasa managers have decided that the failure of a heater used to keep propellant from freezing in a firing thruster will not affect the go-ahead for lift-off. The thruster is not used during launch but can control the shuttle's orientation in orbit and during a rendezvous with the space station.
The process of loading the bright orange, 15-storey-tall external fuel-tank with more than 500,000 US gallons (two million litres) of cryogenic liquid oxygen and liquid hydrogen began shortly before 0600 EDT (1000 GMT) on Saturday.
The astronauts were cheered as they left for the launch pad
There is much at stake for the mission. In the eyes of some observers, the shuttle still has to prove its safety as a launch system following the disastrous loss of the Columbia ship and its crew of seven in February 2003.
A suitcase-sized chunk of insulation foam broke away from Columbia's external tank on lift-off and punched a hole in the vehicle's wing.
This allowed super-heated gases to get inside the orbiter's structure and tear it apart as it made its descent towards Earth.
Foam was also shed during the first post-Columbia launch in July 2005, and engineers have made further modifications to the tank. Managers at the US space agency Nasa are confident the changes meet the standards required and have passed Discovery as fit to fly.
DISCOVERY SHUTTLE FLIGHT
Mission known as STS-121
Discovery's 32nd flight
18th orbiter flight to ISS
Lift-off: 1549 EDT, 1 July
Location: Kennedy Space Center, Launch Pad 39B
Objective: To test new safety equipment and procedures
Payload: Cargobay has 12.75t of equipment and supplies
Crew: Lindsey, Kelly, Fossum, Nowak, Wilson, Sellers, Reiter
"I very strongly feel that we are not risking crew for foam, or I wouldn't feel comfortable launching," said Nasa Administrator Mike Griffin on Friday.
Another vehicle loss would almost certainly shut down the shuttle programme, which is due to be retired anyway in 2010. It would also leave the half-finished ISS project in crisis as the orbiter fleet has been integral to its construction.
Nasa has plenty of time to get Discovery airborne.
The demand for a daylight lift-off combined with the right orbital opportunity to reach the ISS affords the ship a launch window that runs until 19 July.
Beyond that date, Discovery would have to wait for an August slot which is currently earmarked for a flight by the Atlantis shuttle.