US astronaut Scott Kelly and Russian cosmonaut Mikhail Kornienko are about to undertake a 12-month tour of duty on the International Space Station.
It will be the longest continuous stay anyone has had aboard the 400km-high orbiting platform.
Scientists hope to get a keener idea of the effects on the human body of living in microgravity for extended periods.
The space agencies say the data will be invaluable as they plan towards eventually mounting a mission to Mars.
Kelly and Kornienko will launch from Baikonur in Kazakhstan in a Soyuz vehicle at 01:42 local time, Saturday (19:42 GMT Friday).
They will be joined on the flight up by cosmonaut Gennady Padalka, but his tour will only last the normal six months.
Arrival at the ISS should occur about six hours after lift-off.
Although Kelly and Kornienko will set an endurance record for this space station, some of the stays aboard the old Russian Mir platform were much longer.
Four cosmonauts lived on Mir at various times for more than a year, with Valeri Polyakov spending a mammoth 437.7 days in orbit in 1994-95.