Prime Minister Benjamin Netanyahu vowed not to allow Iran to establish a military presence in Syria, after Israel launched air raids on what it said were Iranian targets in its Arab neighbour.
"Israel wants peace but we will continue to defend ourselves with determination against any attack on us and against any attempt by Iran to entrench itself militarily in Syria or anywhere else," he said.
Netanyahu's remarks came as he convened his security chiefs for consultations on Saturday's confrontations which followed Israel's interception of what it said was an Iranian drone launched from Syria.
Israel then launched air attacks on the drone's control systems, with Syrian anti-air fire bringing down an F16 fighter in northern Israel.
The Israeli air force launched a further series of strikes targeting what it said were Iranian and Syrian military targets in Syria.
"Israel holds Iran and its Syrian hosts responsible for today’s aggression," Netanyahu said.
"We will continue to do whatever is necessary to protect our sovereignty and our security."
Iran, for its part, denounced Israeli "lies" and said Syria had the right to "legitimate self-defence" in response to air strikes launched by Israel.
The Israeli leader said he had spoken with Russian President Vladimir Putin whose country supports the Syrian regime.
"I reiterated our right and duty to defend ourselves against attacks from Syrian territory," Netanyahu said, adding that the two leaders agreed to continue their coordination on Syria.
Netanyahu also said he spoke with US Secretary of State Rex Tillerson.