Russian bombers flying from an Iranian air base struck rebel targets across Syria on Tuesday, Russian and Iranian officials said, dramatically underscoring the two countries’ growing military ties and highlighting Russia’s ambitions for greater influence in a turbulent Middle East.

The long-range Tu-22 bombers took off from a base near Hamadan in western Iran and launched raids in the Syrian provinces of Aleppo, Deir al-Zour and Idlib, the Russian Defense Ministry said in a statement. The ministry said the bombers were accompanied by Russian fighter jets based in Syria.

Both countries are staunch allies of Syrian President Bashar al-Assad, but the flights marked the first time Russia has launched strikes from Iranian territory.

Iran has long banned foreign militaries from establishing bases on its soil. But the raids appeared to signal a budding alliance that would expand Russia’s military footprint in the region.

Iran and Russia “enjoy strategic cooperation in the fight against terrorism in Syria, and share their facilities and capacities to this end,” Iran’s National Security Council chief, Ali Shamkhani, said Tuesday, according to the state-run Islamic Republic News Agency (IRNA).

State Department deputy spokesman Mark Toner called the flights “unfortunate, but not surprising or unexpected.” Like other Russian strikes in Syria, he said, the Russian bombers predominantly targeted moderate opposition forces fighting against Assad, rather than the Islamic State or other terrorist groups.

“It only makes more difficult what is already a complex, contentious and difficult situation,” Toner said, adding that it was “unclear” whether Russia planned to continue using the Iranian base, or the operation was a “one-off.”

Secretary of State John F. Kerry raised the flights in a Tuesday telephone conversation with his Russian counterpart, Sergei Lavrov, Toner said.

Under the terms of a U.S.-Russia agreement to “deconflict” their flights over Syria, the U.S. military was notified in advance that the bombers would pass across Iraqi airspace and through Syria, according to Col. Christopher Garver, the Baghdad-based spokesman for U.S. forces in Iraq and Syria.

“It was not a lot of time, but it was enough,” Garver said of the notice given. He said the Russian aircraft “did not impact coalition operations in either Iraq or Syria,” where coalition planes are in the air virtually around the clock.

Although several countries in the region have flirted with strengthened ties to Russia, Moscow has made little headway in fulfilling its ambitions for greater Middle East sway. Syria has long been an exception, historically purchasing Russian arms and hosting a Russian naval facility on the Mediterranean.

Tehran, in addition to their joint support for Assad, has seen strategic advantage in relations with post-Soviet Russia, sharing a desire to counter U.S. influence with increased trade and energy cooperation. The Iran nuclear deal allowed Russia to fulfill a years-old agreement to sell Iran its powerful S-300 air-defense missile system.

Last year, Russia and Iran signed a military cooperation deal focused on training and on fighting terrorism. On Sunday, Russian President Vladimir Putin’s top Middle East envoy arrived in Tehran to discuss bilateral relations. Russia has also requested the use of Iranian airspace to fire cruise missiles at rebel targets in Syria.

Shiite-led Iran has sent thousands of troops and fighters, including members of its Revolutionary Guard Corps, to Syria to bolster Assad — who is from the Shiite minority Alawite sect — against largely Sunni rebels. For Tehran, losing a longtime ally to a majority-Sunni uprising would undermine its own influence in the region.

Iranian proxies such as Lebanon’s Hezbollah and an array of Shiite Iraqi militias have also fought for the Syrian regime. And last year, Russia began its own operations in Syria, committing tanks, artillery and combat aircraft to the fight. It also built a new air base in Latakia province in the Alawite heartland.

Russian intervention marked a turning point in the fate of the Assad regime, which had been losing ground to rebel forces.

But until now, Russia’s long-range bombers, which require longer airstrips, had to be launched from Russian territory more than 1,200 miles away. Now, those same bombers need to fly only about 400 miles from Iran to Syria, Iran’s Fars News Agency reported Tuesday. The shorter distance, using less fuel and allowing a bigger payload, will allow Russia to intensify its air campaign against rebel-held areas.

Syrian government troops and opposition fighters are now locked in a battle for the strategic city of Aleppo, where residents face a growing humanitarian crisis. Russia has carried out strikes in support of government troops there, activists say.

Russia’s Defense Ministry said Tuesday that its long-range bombers struck targets linked to the Islamic State and Jabhat Fatah al-Sham, a group that formally split from al-Qaeda last month and changed its name from Jabhat al-Nusra. The strikes destroyed five major ammunition depots, training camps and three command posts, the ministry said.

But rights groups have criticized both Russia and the Syrian regime for repeated strikes on civilian targets, including homes, schools and hospitals. Russian and Syrian officials have denied those reports.

On Tuesday, the New York-based Human Rights Watch said Syrian and Russian troops have used banned incendiary weapons in civilian areas.

“These weapons inflict horrible injuries and excruciating pain,” Steve Goose, arms director at Human Rights Watch, said in a statement. “The disgraceful incendiary weapon attacks in Syria show an abject failure to adhere to international law.”

Iran is also deeply involved in conflicts in Yemen and Iraq, where it holds particular influence.

Iran was quick to provide military supplies to the Shiite-led government in Baghdad as Islamic State militants made their land grab in the summer of 2014, pushing toward the capital.

In recent years, Maj. Gen. Qasem Soleimani, commander of the Revolutionary Guard Corps’ elite Quds Force, has made regular appearances on the battlefield in both Iraq and Syria, becoming the public face of Iran’s growing military power.

DeYoung reported from Washington. Loveday Morris in Beirut contributed to this report.