An unmanned American Falcon-9 rocket has broken apart in flames minutes after lifting off from Cape Canaveral in Florida.
Debris from the SpaceX vehicle tumbled out of the sky into the Atlantic Ocean.
The rocket, which had 18 straight successes prior to Sunday's flight, was in the process of sending a cargo ship to the International Space Station.
As well as carrying supplies for the astronauts, the Falcon had also been transporting a new docking port.
"The vehicle has broken up," said Nasa commentator George Diller, as TV images showed the white rocket falling to pieces.
"We appear to have had a launch vehicle failure," he added.
The problem occurred 139 seconds into the flight, just before the first-stage of the rocket was about to separate from the upper-stage, or top segment of the Falcon-9.
"There was an overpressure event in the upper-stage liquid oxygen tank," tweeted SpaceX CEO Elon Musk.
"Data suggests counterintuitive cause. That's all we can say with confidence right now. Will have more to say following a thorough fault tree analysis."
SpaceX will now lead an investigation, overseen by the Federal Aviation Authority and Nasa, which contracts the California company commercially to resupply the station.
This means there will be no further Falcon-9 launches in the immediate future.
"Once we identify the issues we will submit that documentation to the FAA and it will be considered prior to the next flight," said SpaceX president Gwynne Shotwell.
"I don't have a timeline for that right now. It certainly isn't going to be a year - (more likely) a month or so."