Russian warplanes took off from an airbase Tuesday in western Iran's Hamadan province and conducted an airstrike targeting militants in Syria's Aleppo, Deir al-Zour and Idlib regions, Russia's Defence Ministry said.
It was the first time Russian warplanes used an Iranian airbase for military actions in Syria, TASS reported.
A monitoring group reported the deaths of 31 civilians and 12 rebel fighters in airstrikes on Aleppo, Idlib and Deir al-Zour, though it was not clear whether the casualties were in the same Russian strikes from Iran.
"Long-range Tu-22M3 bombers and front-line Su-34 bombers that had taken off with a full load of bombs from an airbase in Hamadan conducted a coordinated attack on targets of the terrorist groups Islamic State and al-Nusra Front," the Russian Defence Ministry said.
Both groups have been designated as terrorist by the United Nations. Last month, al-Nusra Front changed its name to Jabhat Fatah al-Sham.
Russia and Iran are longtime allies of the Syrian government, which has been waging war for more than five years against a range of rebels and militant groups.
The attack hit five large storage facilities housing weapons, munitions and fuel, as well as militant training camps around the cities of Saraqib, al-Bab, Aleppo and Deir al-Zour and three militant command points around the cities of Jafra and Deir al-Zour, the Russian Defence Ministry said.
The United States called the development "unfortunate" but not surprising. State Department spokesman Mark Toner said it only made a complex situation more difficult.
He said it appeared there was no direct assistance from Iran and confirmed that the airstrikes purported to target Islamic State as well as Jabhat Fatah al-Sham targets.
He said that Russia's action "could very well be" a violation of a UN Security Council resolution, which prohibits the supply, sale and transfer of combat aircraft to Iran unless approved in advance by the UN.
The pro-opposition Syrian Observatory for Human Rights reported that 12 rebel fighters were killed in Russian airstrikes on a corridor that the rebels recently opened into the opposition-held eastern sector of Aleppo.
Another 19 civilians were killed in airstrikes on eastern Aleppo's Tariq al-Bab and Sakhour districts, and 12 more were killed in airstrikes on Deir al-Zour and a town in Idlib province, the Britain-based observatory said.
The observatory could not confirm whether those airstrikes were carried out by Russian aircraft or by Syrian government forces, which carry out regular airstrikes and have less accurate targeting than Russia.
The UN Commission of Inquiry on Syria said that it was "gravely concerned for the safety of civilians" in Aleppo, noting that 100,000 children are reported to live in the city's rebel-held east.
The commission warned of intensifying "asymmetric warfare" for opposition-held areas that includes cutting off supply routes in what seems a "prelude to a siege" to force rebels to capitulate.
Human Rights Watch on Tuesday accused Syrian regime forces and their Russian allies of using incendiary weapons, which burn their victims and start fires, in rebel-held civilian areas in north and north-western Syria.
Russian President Vladimir Putin and Iranian President Hassan Rowhani met last week in Azerbaijan to strengthen military ties, according to a Kremlin transcript.
Russian Defence Minister Sergei Shoigu this week said Moscow and Washington were "currently in a very active stage of negotiations" to begin joint military action in Syria against Islamic State.
Toner said Russia's use of the Iranian airbase did not preclude a cooperative arrangement with Russia that would include a cease-fire across Syria, full access to humanitarian assistance and a restart of peace talks in Geneva.
Russia and the US have supported opposing sides in Syria, with the US and some Western and regional powers backing certain rebel groups. However, Russia and the US agree on the need to eliminate UN-designated terrorist groups, such as the Islamic State movement.
Also on Tuesday, moderate opposition factions backed by Turkey said they had captured the border village of al-Rai, north of Aleppo, from Islamic State.
The rebels, who have said the village is a key smuggling route for the extremists, previously took al-Rai in April before being driven out again three days later.