With no end in sight to the conflict now in its 28th month, the grim toll keeps rising -- some 100,000 people have been killed and 1.8 million Syrians are now refugees in neighbouring countries.
Up to four million people are also now believed to have been displaced by the fighting inside Syria's borders, where local aid workers risk their lives daily to cross shifting frontlines to supply vital food and water.
"We are having a very difficult time being able to access people, move people, protect people," Kerry said at the start of the talks in the State Department.
UN and NGO leaders say the Syrian conflict is the worst they have seen since the genocide in Rwanda in 1994.
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Fears are growing the conflict is spilling over the country's borders, destabilising already vulnerable neighbouring countries such as Jordan, Lebanon and Iraq.
He was meeting with the UN High Commissioner for Refugees Antonio Guterres as well as the heads of the World Food Program, UNICEF and the International Red Cross.
The US is the largest single donor to UN-run relief programmes, having already pledged some USD 815 million to help the Syrian refugees.
But unlike in natural disasters, such as earthquakes and tsunamis, charities and non-governmental organisations say appeals for donations from the public are largely falling on deaf ears.
They now have to consider longer term planning for housing and feeding millions of refugees, educating children and caring for daily medical needs, even as they deal with the daily crisis of some 6,000 people fleeing the fighting.