GENEVA — Syria’s opposing sides met face-to-face for the first time in three years for U.N. mediation Thursday, with the U.N. envoy citing a historic chance to end a conflict that has left hundreds of thousands dead, millions displaced and fomented a proxy war by foreign powers.

In a ceremony rich in symbolism, and as violent clashes continued in Syria, Staffan de Mistura convened government and opposition envoys for a new U.N. effort to cobble together a political process to halt suffering for millions of Syrians after nearly six years of war.

“The Syrian people all want an end to this conflict and you all know it,” he said in a cavernous U.N. assembly hall, addressing the warring sides. “They are waiting for a relief of their own suffering, and the dream of a new road out of this nightmare to a real and normal future in dignity.”

He took note of the presence of diplomats from the International Syria Support Group, which unites regional and world powers and is led by the United States and Russia. But Washington has been in political flux and de Mistura has said there’s uncertainty about the Syria strategy of the new Trump administration.

Earlier Thursday, Russian President Vladimir Putin — arguably the most potent international power broker in Syria’s conflict — voiced hope for the success of a political settlement and said it would help defeat the “terrorist malaise.” Islamic State and Jabhat Fatah al-Sham, the al-Qaida branch in Syria, have been excluded from the Geneva talks.

A cease-fire deal crafted by Russia, whose blistering air power has helped Syrian President Bashar Assad’s forces regain key territory, and by Turkey, which supports the Western-backed rebels, has provided the backdrop to the Geneva talks. But that truce is being violated on a daily basis.

Cracking through a lack of trust between the two delegations is a primary obstacle, de Mistura told reporters, saying he doesn’t expect miracles. He also acknowledged “work to be done” to unite the fragmented opposition.

De Mistura says he plans to hold separate talks with the two sides Friday, trying to devise a plan that could lead to talks over governance, a new constitution, and elections sought by the U.N. Security Council.

But the diplomatic initiative in the Swiss city — known as Geneva IV following three rounds that failed amid renewed fighting last year — comes at a time of new violence on the ground in Syria.

“We face an uphill task. It will not be easy. There is a lot of tension and there is a lot suffering that everyone has been bearing, but we must apply ourselves to this task,” de Mistura said. “We do know what will happen if we fail once again: More deaths, more suffering, more atrocities, more terrorism, more refugees.”

On Thursday, Nasr al-Hariri, a senior member of the opposition delegation, singled out Iran as the biggest obstacle to settling the conflict in Syria and urged Washington to stop Tehran.

“The guarantor countries, specifically Russia, failed to control the regime and the militias that fight with the regime. They failed to control Iran,” Hariri said, referring to another key Assad backer. He said Tehran has “spread tens of thousands of sectarian fighters.”

Abdulahad Astepho, a member of the opposition, said rebels would have a greater role in this round of talks, reflecting the changing dynamics inside Syria, where factions are drifting away from the exiled opposition leadership and closer to ultraconservative groups.

On Thursday, activists reported heavy clashes across the southern city of Daraa between pro-government forces and opposition factions headed by an al-Qaida-linked group. Opposition media agencies also reported government air raids around the Hama countryside in central Syria.