Russia's defence ministry says it has used a base in western Iran to carry out air strikes in Syria.
Tupolev-22M3 long-range bombers and Sukhoi-34 strike fighters took off from Hamedan on Tuesday, a statement said.
Targets were hit in Aleppo, Idlib and Deir al-Zour provinces, it added. Local groups said 27 civilians had died.
It is reportedly the first time Russia has struck targets inside Syria from a third country since it began a campaign to prop up Syria's president last year.
Iran is Bashar al-Assad's main regional ally and has provided significant military and financial support since an uprising against him erupted in 2011.
The US State Department said Russia's use of an Iranian base was "unfortunate but not surprising".
Asked about moves towards a possible agreement with Russia to co-operate in fighting so-called Islamic State (IS), a spokesman, Mark Toner, said closer Russian-Iranian ties would not necessarily preclude a deal. But he added: "We're not there yet."
In recent months, senior Russian and Iranian officials have discussed boosting their military co-operation, reports the BBC's Steve Rosenberg in Moscow.
Last week, Russia asked Iran and Iraq to allow Russian cruise missiles to fly through their airspace for attacks on terrorist targets in Syria.