Bloomberg | Donna Abu-Nasr and Gwen Ackerman: Israel launched attacks on Iranian and Syrian positions after it said Iran sent a drone into its airspace Saturday, as the tense situation along the border threatened to escalate into wider violence.

Syria fired anti-aircraft missiles at an F-16 fighter plane inside Israel, causing the pilots to eject, the Israeli army spokesman said in a text message; the pilots were hospitalized with moderate to severe injuries. The confrontation is the most serious escalation between the sides since the Syrian civil war began seven years ago.

The Israel Defense Forces “sees the Iranian attack and the Syrian response as a severe and irregular violation of Israeli sovereignty,” the military said in a statement. “The IDF is monitoring events and is fully prepared for further action.”

The exchange of fire comes amid Israeli warnings that it won’t let Syria become an Iranian base and will intercept weapons shipments bound for Iran-backed Hezbollah militants in Lebanon. Iran and allied militias have fought alongside government troops against rebels and Islamist factions in the Syrian war.

Israel struck 12 targets in Syria, including three air-defense batteries and three Iranian targets, in a “large-scale attack” responding to the drone infiltration, the IDF said. Israel has attacked inside Syria frequently since the civil war there began in March 2011, targeting Syrian military posts and arms shipments bound for Hezbollah. Syria and Hezbollah have threatened to retaliate, but until Saturday their strikes had failed to cause damage.

Israeli Prime Minister Benjamin Netanyahu and Defense Minister Avigdor Liberman were set to meet in Tel Aviv on the Jewish Sabbath to discuss the situation, Israeli media reported. Israel closed its northern air space, a spokeswoman said.

Syria’s state-run SANA news agency said Israel targeted a military post in central Syria and said Syrian air defenses hit more than one plane, although that latter claim was not confirmed by the Israeli side.

Explosions were heard along the Lebanese-Syrian border, Lebanon’s official National News Agency said. In Israel, air raid sirens went off repeatedly in the Israeli-controlled area of the Golan Heights.

The U.K.-based Syrian Observatory for Human Rights, which monitors the civil war through activists on the ground, said the Israeli strikes targeted central and southern Syria and the countryside of Damascus. It said there are reports of casualties, including deaths, among the Syrians and their allies.

The current violence is the first direct engagement between Iran and Israel, said Sami Nader, head of the Beirut-based Levant Institute for Strategic Affairs. “Before it was done through proxies,” for example by the Syrian regime or the Iranian-backed Hezbollah, he said.

“The risk is a direct confrontation between Israel and Iran that will encompass Syria and Lebanon,” Nader added.

— With assistance by Nadeem Hamid