The 140-foot Antares rocket, operated by Orbital Sciences Corp, blew up 15 seconds after liftoff Tuesday, lighting up the night sky and raining flaming debris on the launch site.
No one was injured, but the USD 200 million-plus mission was a total loss.
The blast not only incinerated the cargo, 2½ tons of space station food, clothes, equipment and science experiments dreamed up by schoolchildren, but dealt a setback to the commercial spaceflight effort championed by NASA and the White House even before the shuttle was retired.
Although the cause of the blast is still unknown, several outside experts cast suspicion on the 1960s-era Russian-built engines used in the rocket's first stage.
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Orbital Sciences chairman David Thompson himself said that the Russian engines had presented "some serious technical and supply challenges in the past."
He said he expects the investigation to zero in on the cause within a week or so. The launch pad appeared to have been spared major damage.
"We are certainly disappointed by this failure, but in no way are we discouraged or dissuaded from our objectives," he told investors in a phone conference.
Former NASA Administrator Michael Griffin, who helped spearhead the commercial cargo effort, noted that the Antares rocket was still in development.
He and others associated with the space agency went into the program knowing that failures were likely.
In another few years, NASA hopes to launch astronauts again from US soil, aboard commercially supplied spacecraft. Orbital Sciences has never intended to fly anything more for NASA than cargo.