President George W Bush will announce proposals next week to send Americans to Mars, and back to the Moon.
As ever, cost is a major consideration when sending people into space
Senior US officials say he will also reveal plans for the construction of a permanent lunar space station.
Mr Bush intends to reinvigorate the US space programme following setbacks, including the Columbia shuttle disaster, the officials report.
The manned mission to Mars - where Nasa successfully just landed a probe - is not expected for at least 10 years.
Correspondents say Mr Bush had been expected to propose a bold new space mission as part of his re-election campaign.
Lunar testing ground
The president's father proposed men be sent to Mars when he was in office in 1989 but the project went nowhere due to cost.
"He invoked Columbus as they always do," said Bob Park, of the American Physical Society.
"He said like Columbus 'we dream of shores we've never seen' and went on to propose a return to the Moon and then on to Mars. And that lasted until they got a cost estimate."
Sources say the current president will encourage scientists to prepare for the mission in a decade's time, allowing the costs to be spread over a number of years.
The last time the US had men on the Moon was more than 30 years ago.
As the Moon is just three days away, while Mars is at least six months away, it is thought the former could become a testing ground for space equipment.
"We know more about the Moon and if you want to test technology that is going to keep people alive, it's better to do it on the Moon," Chris Welch, a lecturer in space technology, at Kingston University, UK, told the BBC.
"If anything goes wrong you can get back from the Moon in three or four days."
As part of the Bush space initiative, there will reportedly be more exchanges of technology between the US space agency (Nasa) and the Pentagon.
It is hoped the exploration could lead to new technologies and potential new energy supplies.
"I think it is a historic step to set out a plan that will take decades to achieve and will move people on a permanent basis off the surface of this planet - in the process of making this species a multi-planet species," said John Logsdon, of the Space Policy Institute. "It is certainly a watershed point in history."
Experts say, however, that the costs and commitment required to get people to Mars, or even back to the Moon, should not be understated.
"The cost of a manned enclave on the Moon, I think, is going to make the space station look cheap. That's the only good thing about it," Stanford University's Douglas Osheroff told AP.
In any event, "I think we're still 30 years from going to Mars and if there's any reason to do that, I don't know", he added.
Wholly new rocket and capsule systems would have to be developed.
Although the Moon is relatively close at a distance of 385,000 kilometres, a mission to Mars would require astronauts to live off Earth for several years.
Humans versus robots
The recent flurry of spacecraft that went to the Red Planet took six months to get to their destination and they made good use of the closest alignment of Mars and Earth in 60,000 years.
Astronauts on Mars would have to have access to all the necessary air, food and water to sustain them on the surface for perhaps many months until the proper orbits allowed their safe return to Earth.
"I imagine they would take a rover with them," said Welch.
"They would take several scientists - geologists, astrobiologists. The advantage of human beings is that they are more flexible than robots.
"Robots can do a lot but having multiple trained human beings there would tell us so much more."
Europe has a plan dubbed Aurora which envisages putting people on Mars by about 2030.