Top regional ally Saudi Arabia has said the trip will conclude political and commercial agreements and will help bolster the joint fight against Islamist militants.
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US President Donald Trump has left for Saudi Arabia on his first foreign trip since becoming president.
His eight-day trip will also take in Israel, the Palestinian territories, Brussels, the Vatican and Sicily.
It comes as Mr Trump faces uproar at home following his sacking of FBI director James Comey.
He has strongly criticised the decision to appoint a special counsel to oversee an inquiry into alleged Russian influence on the US election.
The trip takes in the capitals of the three major monotheistic religions - Islam, Judaism and Christianity.
Hours before Mr Trump's arrival, Saudi air defence units said they had brought down a rocket south of the capital, Riyadh, that was fired from Yemen by Houthi rebels.
Saudi warplanes are reported to have carried out retaliatory strikes on targets close to the Yemeni capital, Sanaa.
"We want you to be a superpower" is how a senior Saudi prince recently described to me the Kingdom's message to the United States. From day one, Saudi rulers hailed the arrival of President Trump, and what they believe will be greater US engagement in this region.
There's much talk of "turning the page," on what they saw as President Obama's infuriating retreat in Syria, and his focus on a nuclear deal with Riyadh's main rival, Iran.
Saudi Foreign Minister Adel al-Jubeir admitted to me it was "a diplomatic coup" to claim the first stop on the US President's first foreign visit. Other historic first steps may be taken here too.
Another senior official in the region disclosed that Arab states are now discussing moves to start "normalising" relations with their old arch enemy Israel.
This Riyadh summit will focus on new alliances to confront extremist groups. And Riyadh's overriding goal is to convince the US and others to exert far greater pressure on what it sees as the greatest threat, from Tehran.
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