ISTANBUL, Turkey -- Turkey announced Wednesday that it had fired artillery at Syrian military positions in retaliation for mortar rounds from inside Syria that killed five civilians in a house just inside the Turkish border.

It was the first known exchange of fire between Turkey and Syria since a Turkish-backed uprising against Syrian President Bashar Assad began nearly 20 months ago. It was the most serious incident between the two countries since June, when Syria shot down a Turkish reconnaissance aircraft that had violated Syrian airspace.

Turkish Prime Minister Recep Tayyip Erdogan said the Syrian mortar fire landed in Akcakale, a checkpoint in southeastern Turkey that straddles the border with Syria, at 4:30 p.m. local time. Turkish artillery immediately responded, Erdogan said, under standing orders that were rewritten after the June shoot-down.

It was not immediately clear where the Syrian units were that Turkey targeted or what weapons Turkey used to respond. The dead in Akcakale were a mother and her four children, the town’s mayor told Turkish news outlets. Nine other people were wounded.

In a statement, NATO, to which Turkey belongs, “strongly condemned” the Syrian mortar attack and pledged to stand by Turkey. The alliance “demands the immediate cessation of such aggressive acts against an ally and urges the Syrian regime to put an end to the flagrant violations of international law.” But it stopped well short of issuing a threat or saying what steps would follow another incident.

Secretary of State Hillary Clinton said the United States was “outraged that the Syrians have been shooting across the border.” She said the situation in Syria was “very, very dangerous” and called for a cease-fire, an end to the Syrian government “assaulting their own people” and the beginning of a process of political transition.

Syria’s information minister, Omran Zoabi, said Syria was investigating where the mortar rounds that struck Turkey had originated and offered condolences, saying Syria regretted the loss of life. He also urged Turkey and other countries to stop armed rebels from entering Syria.

Tensions have been high along the Syrian-Turkish border for months, as rebels battling to topple the Assad government have seized a series of border crossings, including, most recently, Akcakale. Turkish news media reported that there has been fighting in the border area for the past three weeks, but it was not clear whether there was combat on Wednesday.

On Friday, after mortars damaged 20 properties and injured three civilians in Akcakale, Turkey formally complained to Syria, and the country’s foreign minister, Ahmet Davitoglu, publicly warned that Turkey would respond if there were another incident.

Erdogan’s announcement of the retaliatory strike came six hours after three mortar rounds landed in Akcakale.

“This abhorrent attack was responded to by our armed forces in the border region immediately,” Erdogan said in a statement. “Syrian positions, detected by radar, were fired upon with artillery.”

Erdogan’s statement said Turkey’s response was in line with the military’s rules of engagement, a set of standing orders on the time and circumstances for using lethal weapons, revised after the June shoot-down.

He said that under its own rules of engagement and international law, Turkey “will never leave such provocations against our national security by the Syrian regime unanswered.”