An aid convoy left the Syrian capital Damascus on Monday for the rebel-held town of Madaya, where residents are reported to be suffering from severe malnutrition and a number have already died of hunger.
Some 330 tonnes of food and medical aid were being sent to Madaya, enough to last for about 40 days, a Syrian Red Crescent source said.
Located about 25 kilometres north-west of the capital, Madaya has been under siege since July by forces loyal to Syrian President Bashar al-Assad, aided by fighters from the allied Lebanese Shiite Hezbollah movement.
Another convoy set off earlier in the day to make its way through rebel-held territory in north-western Syria to the isolated government-held villages of Foua and Kafraya, besieged by Islamist rebels.
Pictures circulated on social media by Madaya activists, showing what were said to be starving children and the emaciated bodies of victims of the siege, have caused a global outcry.
Medical charity Doctors without Borders says that 23 people have died of starvation in the town's hospital since the beginning of December.
The group warned that regular supplies to Madaya are essential and a one-time delivery of aid will not be enough.
The town's plight was "a clear example of the consequences of using siege as a military strategy," Doctors Without Borders said.
At least one person has also died due to lack of food and medical supplies in Foua and Kafraya, according to the Syrian Observatory for Human Rights.