Standing with Israeli Prime Minister Benjamin Netanyahu at the White House, Obama condemned the killings on Tuesday of four Israelis who were shot while traveling near the West Bank city of Hebron. Hamas, which rejects Israel's right to exist and opposes peace talks, claimed responsibility.
Netanyahu thanked Obama for condemning the West Bank attack, saying the killings were carried out by people who don't respect human life and who "trample human rights into the dust and butcher everything they oppose."
Both leaders said their opening talks on Wednesday morning - part of a series of separate discussions that also were to include Palestinian President Mahmoud Abbas - were productive. Obama said he would comment in more detail later in the day.
After Obama's sessions with the leaders of Jordan and Egypt, the five men were to gather for dinner.
Formal negotiations between the Israeli and Palestinian leaders are to begin Thursday at the State Department, with Secretary of State Hillary Rodham Clinton as host. Clinton has spent months coaxing the parties back to the bargaining table.
It will mark the first face-to-face negotiations between the Israelis and Palestinians since December 2008. But the two sides are far apart on all key issues, so major progress in the early going is seen as unlikely.
The killing of the four Israeli settlers pointed up the tensions that will probably test Obama's diplomacy.
West Bank settlers said Wednesday they will break a government freeze on construction in their communities to protest the attack.
In addition to his sessions with Abbas and Netanyahu, Obama was meeting with Jordan's King Abdullah II and Egyptian President Hosni Mubarak. Jordan and Egypt are the only two Arab nations that have peace agreements with Israel.
Former Sen. George Mitchell, Obama's special Mideast peace envoy, said Tuesday that the goal of reaching a Palestinian-Israeli deal within one year is intended to counter a sense among many in the Mideast that years of inconclusive negotiations mean the process is never-ending.
American officials are hopeful they can at least get the two sides to agree to a second round of talks, likely to be held in the second week of September in Egypt. That could be followed by another meeting between Obama, Netanyahu and Abbas on the sidelines of the U.N. General Assembly near the end of the month, they said.
Talking to reporters on his plane heading for Washington, Abbas called for decisive American involvement in the talks. He said that if the two sides reach a deadlock, the Obama administration should present "proposals to bridge the gap between the two positions."
One major immediate challenge in the talks will be the Palestinians' demand that Israel extend a 10-month freeze on settlement construction in the West Bank. The freeze expires on Sept. 26.
The Palestinians want a state in the West Bank, Gaza and east Jerusalem - territories Israel captured in the 1967 Mideast war.
Netanyahu, under pressure from his right-wing Likud Party and hawkish coalition partners to resume building inside West Bank settlements when the freeze ends, has made no such pledge. Palestinian officials have warned that without one, the talks in Washington may be nothing more than a two-day excursion to the U.S. capital.
Beyond the settlements, Israel and the Palestinians face numerous hurdles on resolving the other issues of contention, notably the borders of a future Palestinian state, the political status of Jerusalem and the fate of Palestinian refugees.
Also complicating the outlook are internal Palestinian divisions that have led to a split between Abbas' West Bank-based administration and Hamas, which is in control of Gaza. Hamas is not part of the negotiations and has asserted that talks will be futile.
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Associated Press writers Matthew Lee, Ben Feller, Darlene Superville and Julie Pace contributed to this report.