Israeli and US troops were on Sunday beginning a vast missile defence exercise called Austere Challenge 12, in what was hailed as their largest-ever joint military operation, officials said.

The exercise, which involves 3,500 personnel from the US European Command (US EUCOM) and 1,000 Israeli troops and is expected to last three weeks, is likely to send a clear signal to Tehran over its disputed nuclear drive, which must of the West believes is a weapons drive.

"Austere Challenge 12 is the largest aerial defence exercise to take place between the two militaries," an Israeli military statement said.

The long-planned operation comes as the world grapples with the standoff over Iran's nuclear programme, and as a bloody civil war in Syria threatens to set the region alight, although Israel and US officials have said there is no connection.

"These exercises are part of a planned training schedule that seeks to increase cooperation interoperability between the militaries. Planning for the exercise began over two years ago and is not a response to specific events in the region," the statement said.

Of the 3,500 US personnel involved, around a thousand will be stationed in Israel, while the rest will operate in Europe and the Mediterranean, senior US air force officer Lieutenant General Craig Franklin told reporters last week.

Troops will train together on Israel's Iron Dome missile defence system, the latest version of the US Patriot and the Arrow anti-ballistic missile system, jointly developed by the two allies.

Command and control functions will be provided by US Navy Aegis cruiser.

Franklin said the operation, which would last "about three weeks," was a defensive exercise unrelated to Iran, or any other developments in the Middle East.

"While the scenario is driven by the overall situation in the Middle East, AC12 is not related to any specific current event... nor to any perceived tensions in the Middle East," he said.

The cost of the exercise is around $38 million, with Washington covering around $30 million of the total.