The confrontation was the most serious between arch foes Israel and Iran since Syria's civil war began in 2011.

Israel's raids came after it intercepted what it said was an Iranian drone entering its airspace from Syria, calling it an "attack".

It was the first time Israel has publicly acknowledged attacking what it identified as Iranian targets in Syria since the conflict started.

Iran denounced Israeli "lies" and said Syria had the right to self-defence in response to Israeli strikes.

Separately, Iran issued a statement with Syria's other main allies -- Russia and Lebanese militant group Hezbollah -- denying Israel's drone allegations.

Russia's foreign ministry urged "restraint" by all parties, adding it was "unacceptable to create threats to the lives and security of Russian soldiers" in Syria.

Israeli military spokesman Jonathan Conricus warned that Syria and Iran were "playing with fire", but stressed his country was not seeking an escalation.

"This is the most blatant and severe Iranian violation of Israeli sovereignty in the last years," Conricus told journalists.

Israel said its reprisals after the exchange were "large-scale" raids that attacked Syrian air defence systems and Iranian targets.

"Twelve targets, including three aerial defence batteries and four Iranian targets that are part of Iran's military establishment in Syria were attacked," a military statement said.

Israel has repeatedly warned against the presence of Iranian forces in neighbouring Syria.

- 'Massive' fire -

The two crew from Israel's crashed F16 were alive, although one was severely wounded, the military said.

Israel's military said the confrontation began with the drone entering its airspace before being intercepted by a combat helicopter.

Conricus said it was intercepted well inside Israel north of the city of Beit Shean, near the border with Jordan.

He did not say whether the drone was armed or for reconnaissance, but alleged it "was on a military mission sent by Iranian military forces" from an "Iranian base" in the Palmyra area.

Eight Israeli aircraft then "targeted the Iranian control systems in Syria that sent the UAV" and confirmed hits, Conricus said.

He said the aircraft met "massive Syrian anti-air fire", and the F16 later crashed in northern Israel's Jezreel valley.

Conricus said it probably crashed as a result of the anti-aircraft fire.

According to the military, the pilots ejected, landed in Israel and were taken to hospital.

Syria said its air defences repelled two Israeli raids on its military bases in the centre of the country, hitting more than one warplane during the first.

- 'Nobody tries us' -

The Syrian Observatory for Human Rights, a Britain-based monitor of the seven-year civil war, said the earlier Israeli raids had targeted several bases in the east of the central province of Homs.

It said the bases are used by both Iranian and Russian military personnel deployed in support of the regime.

Syrian state media said the later raids targeted positions in the south.

Iranian foreign ministry spokesman Bahram Ghasemi said that "to cover their crimes in the region, Israeli officials are resorting to lies against other countries".

He said "Iran does not have a military presence in Syria, and has only sent military advisers at the request of the Syrian government".

The statement from Iran, Russia and Hezbollah dismissed Israel's drone allegations as "lies".

It said Israel's strikes had targeted drones used against "terrorist organisations", mainly the Islamic State group.

The statement vowed a "relentless response" to "all further aggression".

Danny Danon, Israel's ambassador to the UN, said in a letter to the Security Council that Saturday's events prove Israel's warnings about "Iran's dangerous actions that undermine the situation in our region".

"I call on the Security Council to condemn this dangerous act and to put an immediate end to Iranian provocations," Danon said.

Earlier, Prime Minister Benjamin Netanyahu met officials including Defence Minister Avigdor Lieberman and military Chief of Staff Gadi Eisenkot.

The premier has held a series of talks in recent months with Russian President Vladimir Putin on Iran's influence in Syria and Lebanon.

Netanyahu has sought to persuade Russia to limit Iran's presence near Israel and to stop it from entrenching itself militarily in Syria.

Israel remains technically at war with Syria and occupies a swathe of the strategic Golan Heights that it seized in the Six-Day War of 1967 and later annexed in a move never recognised by the international community.

Israel has sought to avoid direct involvement in the Syrian war, but acknowledges carrying out dozens of air strikes there to stop what it calls deliveries of advanced weaponry to Hezbollah.

Analysts said they did not expect a further escalation for now, but suggested the heavy anti-aircraft fire showed Syria was more emboldened to counter Israel's strikes.

Ofer Zalzberg of the International Crisis Group said Russia should mediate since "it is the only stakeholder which has strong relations with all sides today".

But he said "this incident signals a new phase in a way of the war in Syria".