Pope Francis has called for an end to the "increasingly unacceptable" Palestinian-Israeli conflict during a visit to the West Bank city of Bethlehem.
His comments came as he met Palestinian leader Mahmoud Abbas as part of a three-day tour of the Middle East.
He is holding an open-air mass for 8,000 local Christians by Bethlehem's Church of the Nativity.
The tour's official purpose is to improve ties with the Orthodox Church.
Later, the Pope will travel to Tel Aviv and then Jerusalem where he will meet Bartholomew I, the Orthodox Patriarch of Constantinople.
However, correspondents say Palestinians are hoping for a show of support as his visit comes just weeks after peace talks with Israel broke down.
Palestinian officials have already noted that Pope Francis is the first pontiff to travel directly to the West Bank rather than enter via Israel.
Many Palestinians see it as a recognition of their push for full statehood.
Speaking in Bethlehem on Sunday, the Pope said: "The time has come to put an end to this situation which has become increasingly unacceptable."
He talked of the "tragic consequences of the protracted conflict" and the need "to intensify efforts and initiatives" to create a stable peace – based on a two-state solution.
Pope Francis has insisted the purpose of his Middle East trip is purely religious.
However, the first speech on his arrival in Bethlehem showed that he is also willing to address pressing political issues, says the BBC's Yolande Knell in Bethlehem.
On his way to Manger Square where he is holding an open-air mass, he stopped to look at a high concrete wall that is part of the barrier Israel is building in and around the West Bank.
Israel says it is needed for security but the Palestinians see it as a land grab, our correspondent adds.
During the afternoon, Francis will take a short flight to Tel Aviv where he will be formally welcomed to Israel by President Shimon Peres before flying on to Jerusalem.
Israel has issued restraining orders against several Jewish right-wing activists this week over concerns that they could try to disrupt the visit.
Twenty-six people were arrested overnight for throwing stones and bottles at police during a protest at a holy site on Mount Zion, reports say.
In Jerusalem, the Pope will commemorate the 50th anniversary of a historic meeting of Catholic and Orthodox leaders who moved to end 900 years of division between the two churches.
The Pope's tour began on Saturday with a visit to Jordan.
He was welcomed by King Abdullah II. In a speech at the royal palace, he stressed the need for an "urgent" solution to the Syrian conflict.
He praised Jordan for its "generous welcome" to Syrian refugees.
On Monday the Pope is due visit the al-Aqsa mosque complex in Jerusalem's Old City followed by the Dome of the Rock and the Western Wall.
Pope Francis will be the fourth leader of the Roman Catholic Church to visit Jerusalem, after Popes Paul VI, John Paul II and Benedict XVI, who went there in 2009.