French anti-terrorist officers are searching for 28kg (61lb) of Semtex explosive missing from a depot in the suburbs of the city of Lyon.
France's interior ministry confirmed an investigation was underway, saying the manager of the site had been suspended.
Semtex is a powerful explosive favoured by terrorist groups as it is odourless and practically impossible to detect.
Police said detonators were also missing and that they are treating the theft "very seriously".
The depot, in a disused 19th century fort at Corbas, is used for storing explosives by a civil defence unit charged with the job of blowing up bombs and ammunition left over from the two world wars.
Police said the discovery that the Semtex was missing was made on Friday but admitted the explosives could have been taken up to a week ago.
In a statement released late on Friday the interior ministry said there had been "security failings" which had made the theft possible.
Police sources have declined to confirm a newspaper website report which said that the store had been unguarded.