A U.S. envoy is heading to the Middle East to urge calm between Israel and Palestinians.

A senior American diplomat is headed to the Middle East to meet with Israeli and Palestinian leaders “to urge de-escalation and to bring calm,” Secretary of State Antony J. Blinken said on Wednesday amid mounting violence.

Speaking at the State Department in Washington, Mr. Blinken repeatedly affirmed Israel’s right to defend itself from rocket attacks from Hamas, the Islamist militant group that runs the Gaza Strip.

“There is, first, a very clear and absolute distinction between a terrorist organization, Hamas, that is indiscriminately raining down rockets, in fact, targeting civilians, and Israel’s response, defending itself,” Mr. Blinken said.

But he also said Israel “has an extra burden” to try to prevent civilian deaths, noting that Palestinian children have been killed in Israeli strikes.

“Whenever we see civilian casualties and, particularly, when we see children caught in the crossfire, losing their lives, that has a powerful impact,” said Mr. Blinken, sounding anguished. He added: “The Palestinian people have the right to safety and security, and we have to, I think, all work in that direction.”

Mr. Blinken said he was deploying Hady Amr, the deputy assistant secretary of state for Israel and Palestinian affairs, to meet with leaders from both sides in coming days. Mr. Amr was expected to depart Washington later Wednesday for the region.

At the Pentagon, Defense Secretary Lloyd J. Austin III also offered “ironclad support” for Israel’s right to self-defense during a conversation earlier Wednesday with Israel’s defense chief, Benny Gantz.

A readout of their talk, issued by John Kirby, the Pentagon press secretary, said Mr. Austin had condemned the rocket attacks by Hamas, and urged calm among all parties, but did not mention the matter of casualties among Palestinian civilians.

President Biden took office this year with little interest in pursuing an Israel-Palestinian peace agreement, given the failure by previous presidents from both parties to foster a lasting accord. But the latest outbreak of violence has prompted growing calls from within the Democratic Party for Mr. Biden to play a more active role.

The Biden administration has endorsed of a two-state solution but, experts said, has made little effort to push the parties toward one.

“The problem with the Middle East,” said Martin S. Indyk, a special envoy for Israel-Palestinian negotiations during the Obama administration, “is that you can try to turn your back on it, but it won’t turn its back on you.”

On Wednesday, Mr. Blinken repeated anew that the United States remains committed to a two-state solution. “This violence takes us further away from that goal,” he said.

Mr. Blinken later said he also had spoken with Prime Minister Benjamin Netanyahu of Israel to reinforce his message: “It’s vital now to deescalate,” Mr. Blinken said on Twitter.

Michael Crowley contributed reporting.

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