An Israeli rocket strike early on Sunday hit a building in central Damascus's Kafr Sousa neighborhood near a large, heavily guarded security complex close to Iranian installations, killing five people, witnesses and officials said.
A police official said on state media that there were several casualties and injured.
An Israeli military spokesperson declined to comment.
Citing a military source, state media said Israel had carried out air strikes targeting several areas in the capital shortly after midnight, causing five deaths and 15 injuries among civilians, and damage to several residential buildings.
"It caused damage to several civilian homes and material damage to a number of neighborhoods in Damascus and its vicinity," the army said in a statement.
The rare, targeted strike damaged several buildings in the densely populated district close to Omayyad square in the heart of the capital, where multi-story security buildings and Iranian institutions are located within residential areas.
It was not immediately clear whether the strike was aimed at a specific individual.
Pro-Iran Hezbollah's top commander Imad Moughniyeh was killed in 2008 in a bombing in Kafr Sousa, a heavily policed area where residents say several Iranian security agencies are located, including a major cultural center.
For almost a decade, Israel has been carrying out air strikes against suspected Iranian-sponsored weapons transfers and personnel deployments in next-door Syria. Israeli officials have rarely acknowledged responsibility for specific operations.
Iran has expanded its military presence in Syria in recent years and has a foothold in most state-controlled areas, with thousands of members of militias and local paramilitary groups under its command, Western intelligence sources say.
Israel has also in recent months intensified strikes on Syrian airports and air bases to disrupt Iran's increasing use of aerial supply lines to deliver arms to allies in Syria and Lebanon, including Lebanon's Iran-backed Hezbollah.
The strikes are part of an escalation of what has been a low-intensity conflict whose goal was to slow down Iran's growing entrenchment in Syria, Israeli military experts say.
Iran's proxy militias, led by Lebanon's Hezbollah, now hold sway in vast areas in eastern, southern and northwestern Syria and in several suburbs around the capital.
Syrian President Bashar al-Assad's government has never publicly acknowledged that Iranian forces operate on his behalf in Syria's civil war, saying Tehran has only military advisers on the ground.