The Atlantis shuttle is set to dock with the International Space Station (ISS) on Sunday.
It will be the orbiter's final visit before it and the rest of Nasa's reusable spaceplane fleet are retired.
Although a swan-song, the sortie to the ISS is anything but a farewell tour.
Atlantis is carrying a huge supply of food that could be critical to the orbiting outpost's future operation, and the ship's crew will have a busy few days off-loading the cargo.
Just before the docking, the shuttle will perform the now traditional back-flip manoeuvre that allows the station's residents to photograph the vehicle's belly.
The imagery will be sent to the ground where engineers can check if Atlantis sustained any damage during its launch on Friday.
Attachment to the ISS is expected at 1507 GMT on Sunday. The ship is due to spend at least seven days at the platform.
It is carrying the Raffaello Multi-Purpose Logistics Module, a large cylinder that is packed with over 3.5 tonnes of food, other supplies and spare parts that should sustain the station for about a year.
This will be lifted out of the shuttle's payload bay and attached directly to the station on Monday.
The Atlantis and ISS crews will then be able to go inside Raffaello to begin the process of transferring its contents to more permanent storage positions on the platform.
The delivery has major significance. Once Nasa retires its shuttles, it will be relying on robotic spacecraft from private companies to make cargo runs to the ISS.
But these vehicles have yet to prove themselves, and the Atlantis shipment provides some margin if the commercial freighters are late in their development or experience a failure.
Just one spacewalk will be performed during this mission.
This will be done by two of the station's residents, who will move an ammonia pump that recently failed on the station to the shuttle's payload bay.
The pump is an important component in the ISS cooling system and it will be taken back down to the ground so engineers can understand why it stopped working.
Atlantis should return to Earth on Wednesday 20 July. The early morning landing will bring to an end Nasa's 30-year orbiter programme.
Atlantis itself will be made safe for public display at the Kennedy Space Center visitor complex.
The US space agency will then use Russian rockets and capsules to get its astronauts to the station.
This arrangement will last until American companies bring forward a range of new vehicles to transport crew to low-Earth orbit.
None of these will be ready until 2014 at the absolute earliest.
Nasa intends to use resources diverted from the shuttles to build a capsule capable of going to deep-space locations such as asteroids.
It will need a big new rocket for such missions, also. The design concept for this launcher is expected to be announced before the end of the summer.
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