Israel launched its largest-ever air offensive against its old adversary in an attempt to stop it from developing a nuclear weapon, and Iran and Israel targeted one other with missiles and airstrikes early Saturday.

As waves of Iranian missiles sped across the skies and Israeli interceptors arose to meet them, air raid sirens wailed throughout Israel, including in Jerusalem and Tel Aviv, sending locals running for cover.

A missile that landed close to their homes in Israel killed a man and a woman and injured many more, according to Israel’s ambulance service.

Rescue teams were searching the rubble of apartment buildings that were destroyed in Rishon Lezion, a city outside of Tel Aviv.

Israel’s Defence Minister, Israel Katz said on Saturday the Iranian leadership had crossed a red line by firing at civilians and will “pay a heavy price for it”.

A missile fired from Yemen by the Iran-backed Houthi militia, killed five Palestinians including three children in the Israeli-occupied West Bank, according to the Palestinian Red Crescent.

Iran’s U.N. envoy Amir Saeid Iravani said 78 people, including senior military officials, have been killed in Israel’s strikes on Iran and more than 320 wounded, most of them civilians.

Tehran launched waves of airstrikes on Saturday after two salvos on Friday night, Fars reported.

Those were in response to Israel’s attacks on Iran early on Friday against commanders, nuclear scientists, military targets and nuclear sites. Iran denies that its uranium enrichment activities are part of a secret weapons programme.

On Friday, the United States military assisted in shooting down Iranian missiles aimed toward Israel, according to two American officials.

According to Israel’s military, Iran fired less than 100 missiles on Friday, with the majority intercepted or missing their target.

Israeli assaults on Iran throughout the day, as well as Iranian response, fueled fears of a larger regional conflict, despite the fact that Israel has crushed Iran’s allies Hamas in Gaza and Hezbollah in Lebanon.