Children aged three, six and 10, and a 30-year-old religious education teacher were shot dead as they arrived for classes at the Ozar Hatorah school in the southern city of Toulouse.
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The killer, riding a powerful scooter, is suspected of being the same gunman who shot dead three soldiers of Arab origin in two incidents this month in Toulouse and nearby Montauban.
"In France today there was a despicable murder of Jews, including small children," Netanyahu told a meeting of his Likud party.
"It is too early to determine exactly what the background to the murderous act was, but we certainly cannot rule out the option that it was motivated by violent and murderous anti-Semitism."
Israeli Foreign Minister Avigdor Lieberman was "deeply shocked" over the incident, a statement from his office said.
"Only a person possessing demonic evil could conduct such a terrible murder of small children at a school," it quoted him as saying, while parliament speaker Reuven Rivlin said the attack was against Jews and Israel and as such should alert the international community.
The dead teacher was named by a relative as Jonathan Sandler, originally from Jerusalem, who had moved to France last year.
The White House condemned the "outrageous" and "unprovoked" shooting. "We were deeply saddened to learn of the horrific attack this morning," said National Security Council spokesman Tommy Vietor.
Residents near scene of Toulouse attack (Photo AFP)
European Commission president Jose Manuel Barroso said: "I strongly condemn this odious crime and express the horror that this blind violence inspires. Nothing is more intolerable than the murder of innocent children."
The Vatican voiced outrage, with spokesman Federico Lombardi condemning the "horrific and heinous act," noting that it followed other "senseless violence" in France.
Italian Prime Minister Mario Monti also expressed "outrage and alarm," and stressed that "anti-Semitism, xenophobia and intolerance are utterly contrary to the . . . values that underlie all of humanity".
European Council President Herman Van Rompuy denounced it as an "odious crime," Spanish Prime Minister Mariano Rajoy said he was "shocked by the cruelty," and his Belgian counterpart voiced his "horror and indignation."
German Foreign Minister Guido Westerwelle said he was "deeply shocked," adding: "I hope the perpetrators are found quickly and are called to account."
"Anti-Semitism and violence against Jewish institutions or people of Jewish faith have no place in Europe and must be rigorously punished," he added.
Poland's foreign ministry said: "Such acts of terror can have no justification and must be condemned unreservedly by the civilized world.
Belgium and the Netherlands both stepped up security around Jewish schools and other buildings, while European Jewish groups urged France to catch the gunman.
"While many of the details are still emerging, it appears that this was a premeditated attack with the intention to murder Jewish children," said Moshe Kantor, president of the European Jewish Congress.
"Whoever did this is looking to target the Jewish community at its weakest point, its youth, in the hopes of spreading fear throughout the community," Kantor said.
"They will not succeed, the Jews of Europe in general and the Jews of France in particular have a long history of standing firm against hatred and violence," he added.
The Brussels-based Rabbinical Center of Europe (RCE) said: "It is difficult to believe that the main challenge to European Jewry remains anti-Semitism and threats to their lives."
RCE deputy director Rabbi Aryeh Goldberg added: "This act of barbarity and murder will be met with a Jewish response.
"We will bury the dead, look after the injured, and we will demand that justice is pursued through the appropriate channels," he said.
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