California's SpaceX company will try to soft-land part of its Falcon rocket when it launches a cargo mission to the space station on Tuesday.
All segments of a rocket are usually discarded after use and are destroyed as they fall back to Earth.
SpaceX, however, has been practising the controlled return of the first stage of its Falcon 9 vehicle.
It now wants see if it can target the booster at a sea barge positioned in the Atlantic, off the coast of Florida.
If it succeeds in bringing the stage to a stable vertical stop, it could point the way to a revolution in rocketry that dramatically lowers launch costs.
SpaceX itself is playing down expectations, rating the chances of success at no more than 50-50.
"I'm pretty sure this will be very exciting, but, as I said, it's an experiment," cautioned Hans Koenigsmann, vice president for mission assurance at SpaceX.
"There's a certain likelihood that this will not work out all right, that something will go wrong. It's the first time we have tried this - nobody has ever tried it as far as we know."
Lift-off for the Falcon 9 from Cape Canaveral is scheduled for approximately 06:20 local Florida time (11:20GMT).
The primary purpose of the flight is to send the Dragon cargo ship on a path to rendezvous with the International Space Station (ISS) on Thursday.
It will be the first American re-supply mission to the orbiting platform since October's spectacular explosion of a freighter system operated by competitor Orbital Sciences Corporation.
But as important as Tuesday's mission is to the servicing of the ISS, it is the outcome of the SpaceX experiment that is likely to make the headlines.
Traditionally, rockets have had an expendable architecture.
As they head skyward, they dump engines and empty propellant tanks to save the weight that allows their upper stage, including the satellite payload, to make the jump to orbit.
Any discarded hardware simply tumbles back towards the planet and is torn apart.
And this approach means every new mission needs an expensive new rocket.
SpaceX, on the other hand, believes it can return, refurbish and re-use key elements of its rockets.
To this end, it has been testing first-stage boosters that relight their engines to try to slow their fall through the atmosphere, attaching fins to help guide them downwards, and legs to make a stable touchdown.
So far, there have only been mock landings, in which the stage is brought to a hovering position at the surface of the ocean, where, without a solid platform to set down, every booster has subsequently been lost in the water.
Tuesday's experiment will be different in that SpaceX has sent a floating barge to the targeted return site some 300km northeast of the Cape.
Getting the stage to arrive at the exact location will be an immense challenge.
The "drone ship" is less than 100m wide, and for all the experiments SpaceX has conducted to date it has been working on a landing accuracy of some 10km.
What is more, the barge must cope with waves and currents, and will have to use thrusters to maintain a steady station.
But SpaceX sees reusability as a goal for the long term, and it will keep working to improve the performance and reliability of its recovery technologies.
Real-time video coverage of the landing is not expected. SpaceX says it does not have the telecommunications infrastructure in place to do that, and, in any case, its primary focus will be on the ISS cargo run.
"Nominal shutdown of the first-stage booster is nine minutes after lift-off," Mr Koenigsmann explained.
"It's actually just a little ahead of Dragon deploy (from the rocket's upper stage), and we will in the webcast concentrate on the Dragon and the main mission."
Of course, to some extent the rocket industry has been here before.
The space shuttle was designed as a partially reusable system, but the complexities of refurbishment in the end provided no savings.
And a number of commentators have also wondered if satellite operators will really want their very expensive spacecraft launched on what would essentially be second-hand rockets.
But SpaceX's activities are certainly making the industry sit up.
It already offers commercial launch prices that undercut its competitors, and Europe has been so alarmed by the California company's progress that it has ordered a new, lower-cost version of its Ariane rocket.
Jonathan.Amos-INTERNET@bbc.co.uk and follow me on Twitter: @BBCAmos