The "dissent channel cable" was signed by 51 mid to high level State Department officers involved with advising on Syria policy.
It was first reported by the Wall Street Journal.
The cable calls for "targeted military strikes" against the Syrian government in light of the near collapse of the cease fire brokered earlier this year, the Journal reported, citing copies of the cable it had seen.
Military strikes against the Assad government would represent a major change in the Obama administration's longstanding policy of not taking sides in the Syrian civil war.
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One US official, who did not sign the cable but has read it, told Reuters the White House remained opposed to deeper American military involvement in the Syrian conflict. The official said the cable was unlikely to alter that, or shift Obama's focus from the battle against the persistent and spreading threat posed by the Islamic State militant group.
A second source who has read the cable said it reflected the views of US officials who have worked on Syria, some of them for years, and who believe the Obama administration's policy is ineffective. "In a nutshell, the group would like to see a military option put forward to put some pressure on the regime," said the second source, who spoke on condition of anonymity.
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The cable discussed the possibility of air strikes but made no mention of adding US ground troops to Syria.
The United States is believed to have roughly 300 US special operations forces in Syria carrying out a counter terrorism mission against Islamic State militants but not targeting the Assad government.
Central Intelligence Agency Director John Brennan told a congressional hearing on Thursday that Assad was in a stronger position than he was a year ago, bolstered by Russian air strikes against moderate opposition. Brennan also said Islamic State's "terrorism capacity and global reach" have not been reduced.
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The names on the memo are almost all of mid level officials many of them career diplomats who have been involved in the administration's Syria policy over the past five years, at home or abroad, the New York Times said. While dissent cables are not unusual, the number of signatures on this document is extremely large, if not unprecedented, according to the Times.
"We are aware of a dissent channel cable written by a group of State Department employees regarding the situation in Syria," State Department spokesman John Kirby said in an email. "We are reviewing the cable now, which came up very recently, and I am not going to comment on the contents."
Kirby said the "Dissent Channel" was an official forum that allows State Department employees to express alternative views.
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