JERUSALEM — Massively retaliating for what it said was an Iranian military strike across the Golan Heights, Israeli forces unleashed a heavy bombardment against Iranian military positions across Syria on Thursday, in a significant escalation that has brought the two long-hostile Middle East heavyweights to the brink of open war.

The U.S. and a number of European powers quickly endorsed what they said was Israel’s right to self-defense, while the Russian government and U.N. Secretary-General Antonio Guterres urged both sides to pull back. But Israeli President Benjamin Netanyahu and his aides vowed to strike back hard at what they say are increasing encroachments by Iran and its proxies across the border in Syria.

Israeli Defense Minister Avigdor Lieberman told reporters here that the Israeli missile and airstrikes had hit “nearly all” of Iran’s significant infrastructure sites in Syria. Iran and Tehran-allied militias have been active in Syria supporting the government of ally President Bashar Assad in the country’s seven-year civil war. The heavy Israeli strikes were in response to approximately 20 missiles fired from inside Syria at Israeli targets in the Golan Heights.

“If it rains on us it will be a flood on them,” Mr. Lieberman said.

Israeli Prime Minister Benjamin Netanyahu said Israel’s military action was intended to send a “clear message” to Tehran to back down, and hinted there may be more to come.

Israel is in “a continuous campaign,” the conservative prime minister said, adding, “Whoever attacks us, we will attack them sevenfold, and whoever prepares to attack us, we will act against them first.”

Already reeling from President Trump’s decision Tuesday to withdraw from the 2015 nuclear accord, Iranian leaders maintained a studied silence in the official media, seen by many as a sign Tehran realizes it is not ready for a direct, open conflict with the powerful Israeli military. A Foreign Ministry spokesman condemned what he called a “violation of Syria’s sovereignty,” without mentioning whether any Iranian forces had been hit in the attacks.

The Syrian military acknowledged that the strikes destroyed a radar station and an ammunition warehouse, and damaged a number of air defense units. It said three people were killed and two were wounded, according to The Associated Press.

The Britain-based Syrian Observatory for Human Rights, which closely monitors the civil war through sources inside Syria, said 23 fighters, including five Syrian soldiers, were killed, the AP reported. It was not immediately clear if any Iranians were among the dead.

In Washington, White House officials strongly condemned Syrian strikes into the Golan Heights, saying that Tehran and its Iranian-trained proxies “bear full responsibility for the consequences of [their] reckless actions” against Israel.

“We strongly support Israel’s right to act in self-defense,” the White House said in a statement Thursday, warning Tehran’s Islamic Revolutionary Guards Corps and its proxy forces in Syria to “take no further provocative steps” toward Israel or other U.S. allies in the region.

Israeli officials claim Tehran has fostered a 80,000-man strong proxy force, trained and equipped by the IRGC, inside Syria and is funneling heavy weapons and material to those forces via the so-called “Shia Crescent” — Iran’s long-sought land bridge linking Iran to Lebanon through Syria and northern Iraq.

The Defense Department remained largely silent on the Thursday’s Israeli airstrikes into Syria, but officials inside the Pentagon remain concerned the ongoing violence between Israel and Iranian-backed regime forces in Syria could bleed over into the U.S.-led coalition against the Islamic State in the country.

‘Shadow war’ no more

In vulnerable parts of Israel, there was a growing concern that the “shadow war” between Tehran and Tel Aviv was about to come out of the shadows.

Just after midnight on Wednesday, Israelis in the Golan Heights heard the familiar sound of wailing sirens beckoning them to bomb shelters. Over the years with the Syrian civil war raging just a few miles away, errant projectiles have fallen on the Israel-controlled side of the border.

But this week’s sirens were different.

Residents of northern Israel have been expecting Iranian-sponsored retaliation for months.

Ilan Shochat, the mayor of Safed, a city in the Galilee, announced that the municipality would open its public bomb shelters on May 8. He said in a statement it was to provide residents a “sense of security.” Representatives of the city, the Israeli Defense Forces’ Home Front Command, social welfare and engineering departments from the Galilee gathered to discuss the preparations.

Israeli authorities have been preparing for a missile attack from Syria or Lebanon over the last 12 years since the inconclusive Second Lebanon War ended. But for many locals there is confidence the army is prepared to defend the country.

Asgeir Ueland, an author and resident of Yesod HaMa’ala on the Jordan River at the base of the Golan, said there doesn’t seem to be a great deal of concern.

“It is more tense than usual. About 11 in the morning we could hear barrages from an artillery exercise on the Golan Heights,” he said.

Children were taken inside amid the rumble from the shells. Tourist bookings for cottages have been canceled and the local town manager met with the military’s Home Front command to discuss preparations.

The rising tensions between Iran and Israel have U.S. commanders on high alert as well, with American forces still on the ground in both Syria and Iraq fighting Islamic State.

American and allied commanders have not taken any additional steps to counter a potentially more aggressive Iranian presence in Syria, Coalition Deputy Command British Army Maj. Gen. Felix Gedney told reporters Tuesday.

“We continually reassess the threat to forces with what’s going on and we will adjust as necessary, [but] we are confident that we will retain the security of our forces operating in Iraq and Syria,” Gen. Gedney said during a teleconference from coalition headquarters in Baghdad.

He declined to comment on what, if any, blowback U.S. or coalition troops based in Syria could face from Iranian-allied forces in Syria, in the wake of Washington’s decision to abandon the Obama-era nuclear deal with Tehran. But the one-star general did say the coalition’s mission in Syria would remain solely focused on defeating the Islamic State, regardless of other conflicts in the region.

U.S. Central Command chief Gen. Joseph Votel, the top commander in the Middle East, conducted a unannounced visit to Tel Aviv last month for face-to-face talks with Lt. Gen. Gadi Eizenkot, general chief of staff for the Israeli Defense Forces.

Defense Secretary James N. Mattis and Israel’s Mr. Lieberman held a private discussion on the growing threat posed to Tel Aviv from Syria and Iran, hours before Syrian military facilities were hit by a round of foreign airstrikes Tuesday.

• Carlo Munoz reported from Washington for this story, which was based in part on wire service reports.

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