The regional officials said Israel had been planning in the days leading up to the airstrike to hit a shipment of weapons bound for the Islamist militant group Hezbollah in Lebanon. They said the shipment included sophisticated, Russian-made SA-17 anti-aircraft missiles, which would be strategically "game-changing" in the hands of Hezbollah.
Hezbollah has committed to Israel's destruction and has gone to war against the Jewish state in the past.
A U.S. official said the strike hit a convoy of trucks.
All the officials spoke on condition of anonymity because they were not authorized to discuss the strike.
The Israeli military declined to comment, and Syrian officials and state media were silent on the issue.
Top Israeli officials have recently expressed worries that if desperate, the regime of President Bashar Assad could pass chemical weapons to Hezbollah or other militant groups. U.S. officials say they are tracking Syria's chemical weapons and that they still appear to be solidly under regime control.
Among Israeli security officials' chief fears is that Hezbollah could get its hands on Syrian chemical arms and SA-17 anti-aircraft missiles. If that were to happen, it would change the balance of power in the region and greatly hinder Israel's ability to conduct air sorties in Lebanon.
Israel suspects that Damascus obtained a battery of SA-17s from Russia after an alleged Israeli airstrike in 2007 that destroyed an unfinished Syrian nuclear reactor.
Earlier this week, Israel moved a battery of its new "Iron Dome" rocket defense system to the northern city of Haifa, which was battered by Hezbollah rocket fire in the 2006 Israel-Hezbollah war. The Israeli army called that move "routine."
The military in Lebanon, which shares borders with both Israel and Syria, said Wednesday that Israeli warplanes have sharply increased their activity over Lebanon in the past week, including at least 12 sorties in less than 24 hours in the country's south.
A senior Lebanese security official said there were no Israeli airstrikes inside Lebanese territory. Asked whether it could have been along the border on the Syrian side, he said that that could not be confirmed as it was out of his area of operations.
He spoke on condition of anonymity because he was not authorized to speak to the media.
A Lebanese army statement said the last of the sorties took place at 2 a.m. local time Wednesday. It said four warplanes which flew in over the southernmost coastal town of Naqoura hovered for several hours over villages in southern Lebanon before leaving Lebanese airspace.
It said similar flights by eight other warplanes were conducted Tuesday.
A Lebanese security official said the flights were part of "increased activity" in the past week but did not elaborate. He spoke on condition of anonymity because he was not authorized to brief the media.
The area of Lebanon where the flights took place borders southern Syria.
Israeli violations of Lebanese airspace are not uncommon and Lebanese authorities routinely lodge complaints at the U.N. against the flights.