The United States on Monday warned Syria not "to even consider using chemical weapons" after Damascus threatened to employ its unconventional arms in the case of outside intervention.
"We have been very strong in our statements inside the US government on the prospective use of chemical weapons and it would be entirely unacceptable," Little said.
The warning by Syrian foreign ministry spokesman Jihad Makdissi comes as Syrian president Bashar al-Assad finds itself fighting desperately pitched battles in Damascus and Aleppo with rebels.
"We would strongly object -- to put it mildly -- to any thinking that would generate a motivation on the part of the Syrian regime to employ these weapons," he added.
Little's remarks come on the heels of a round of meetings between Israeli and US officials on Monday over the deteriorating situation in Syria.
Defense Ministry official Amos Gilad said the Assad government remains in control of its chemical arsenals at this point. Over the weekend, Israeli officials made it clear that Israel was readying options if that changes.
Measnwhile, Israel has lodged a formal complaint with the United Nations over an incursion by some 500 Syrian soldiers and 50 vehicles into the Golan Heights.
IDF officials assured the public they remain vigilant and are keeping careful tabs on events that could impact the security of Israeli civilians.