An unmanned Orbital Sciences Corporation rocket has exploded six seconds after lift-off.
The orbital science rocket was on a resupply mission to the International Space Station, NASA said.
"The Antares rocket suffered an accident shortly after lift-off," NASA mission control in Houston said.
After the countdown, the base of the tall, white rocket ignited on cue, then rose a short distance into the air before it suddenly exploded in a fiery blast six seconds later.
Enveloped in flames, the rocket collapsed to the ground, as a cloud of dark gray smoke rose from the wreckage.
Investigators swiftly secured the perimeter of the area and forbade any outside interviews of witnesses or staff, citing classified equipment that had been aboard the spacecraft.
It is unclear what caused the explosion.
All personnel in the area were accounted for, and there were no reported injuries, the US space agency said.
There was, however significant property damage.
"We have lost the Orb-3 vehicle," said the commentator on NASA television, after the liftoff at Wallops Flight Facility in the US state of Virginia.
"At this point it appears that the damage is limited to the facility," the NASA commentator said.
NASA mission control said the accident occurred just after Orbital's unmanned Cygnus cargo ship blasted off toward ISS carrying 2,200 kilograms of supplies for the six astronauts living at the research outpost.
It was the first nighttime launch of an Antares rocket, said Orbital.
The mission, known as CRS-3, was to be Orbital's fourth trip to the ISS, including an initial demonstration.
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