A campaign of air assaults against Iranian military bases in Syria has been going on for more than a month.
During the civil war, Israel is believed to have carried out hundreds of strikes in Syria, mainly hitting weapons shipments.
Israel said it destroyed almost all of Iran's military infrastructure in the strikes which were launched in response to 20 missiles fired at the Israeli-occupied Golan Heights. "They don't help you, they only harm you, and their presence causes only problems and damage". Thousands of militiamen armed, trained and financed by Iran have also been battling rebel forces alongside Syrian soldiers.
A Syrian war monitor says Israeli strikes on suspected military positions in Syria this week killed 42 people.
Foreign ministry spokesman Bahram Qasemi was quoted on Iranian state TV as saying: "Iran strongly condemns..."
The Iranian economy will still be very badly hit because global banks and companies will be frightened of being punished by the US Treasury, but Iran will not be as isolated politically and economically as it was before 2015.
Syria now relies on a mixture of less advanced Russian-made anti-aircraft systems to defend its air space. The government said the US pullout damages USA credibility on the world stage and the credibility of accords the USA has signed, and puts "the present system of global law in serious danger".
Russian Foreign Minister Sergei Lavrov called for diplomacy between Israel and Iran, and said: "This is a very disturbing trend".
Hamas developed close ties with Iran after the outbreak of the second Palestinian uprising in the early 2000s, with support - both military and financial - peaking following Hamas' victory in the 2006 parliamentary elections.
At the same time, the Kremlin has excluded the connection of the supply of s-300 to Syria with the recent visit of Israeli Prime Minister Benjamin Netanyahu to Moscow, who had urged President Vladimir Putin not to supply the missiles to Syria.
There are some 5000 U.S. troops in Iraq training Iraq's military after the country declared victory over Isis (Islamic State) a year ago.
He added: "Whoever hurts us, we will hurt them sevenfold, and whoever is preparing to hurt us, we will act to hit them first".
On Friday, speaking in northern Israel, Defense Minister Avigdor Liberman sent a message to Syrian President Bashar Assad, telling him to "throw" Iranian forces out of his country.
Danny Danon, Israel's ambassador to the United Nations, called for a UN condemnation of Iran's "acts of aggression" and for the Security Council to "demand that Iran remove its military presence from Syria".
What exactly happened on Thursday?
Reports of unprecedented clashes between Israel and Iran over Syria have sparked calls for restraint from world leaders anxious about the risk of all-out war, even as both sides say they want to avoid a regional conflict.
The Golan Heights is a rocky plateau in south-western Syria, about 50km from the capital Damascus.
Israel captured the Golan Heights in the 1967 war and annexed it in 1981.
What's behind the latest military action?
Russian Federation which is alone in having shut relations with each Iran and Israel has sought to place itself as a mediator to forestall additional escalation.
The White House swiftly condemned Iran's "provocative rocket attacks from Syria against Israeli citizens" and expressed strong support for "Israel's right to act in self-defense", while Russian Federation said the Israeli strikes marked a risky escalation and urged both Israel and Iran to avoid provoking each other.
They included one on an airbase in April that killed seven Iranian troops.
No doubt the revived sanctions will be devastating for the Iranian economy, but Iran has survived a more onerous economic siege in the past while, this time round, ordinary Iranians will be more likely to blame the intransigence of the U.S. rather than that of their own leaders.
Trump said the 2015 nuclear deal that allowed for the lifting of sanctions wasn't tough enough on Iran. European companies, for instance Airbus, are affected too as they buy parts from the US.
"We proceed from the fact that all issues should be solved through dialogue".
"The holy system of Islamic Republic will step up its missile capabilities day by day so that Israel, this occupying regime, will become sleepless and the nightmare will constantly haunt it that if it does anything foolish, we will raze Tel Aviv and Haifa to the ground", the hard-line cleric said during Friday sermons.
The economy of Iran, a big exporter of oil and gas, is likely to be adversely affected.