Security forces rushed to the area following the attack carried out by suspected Tamil Tiger rebels under the cover of darkness, a police official in the area said by telephone.
"We have 15 passengers killed and at least another 38 have been taken to hospital," the official said. "We believe it is the work of the Tigers."
There was no immediate comment from the Tigers who were blamed for a similar bus bombing in the area in June last year when 64 bus passengers were killed.
Wednesday's attacks was in an area some 265 kilometres (165 miles) northeast of the capital Colombo, police said.
The attack against the bus came a week after Tamil Tiger rebels were held responsible for two bomb attacks that killed at least 21 people in Colombo. The attacks came despite a stepping up of the already tight security arrangements across the country amid fears that the Liberation Tigers of Tamil Eelam (LTTE) could avenge military strikes inside rebel-held areas.