Afghan officials say more than 120 schoolgirls and three teachers have been poisoned at a school in the northern Takhar Province.
The attack was blamed on fundamentalist radicals who used an unidentified toxic powder to contaminate the air at the school.
Many victims reportedly lost consciousness and were hospitalized.
One of the children, Samera, told Reuters they originally thought the school's water had been poisoned.
"We saw one of the students was unconscious and in bad condition," she said. "We were told not to drink water but we had already drunk the water and we became unconscious too."
Last month, 150 girls were poisoned in Takhar when they drank contaminated water. And last week, more than 200 boys fell ill at a school in Khost Province.
The Education Ministry reported this month that 550 Afghan schools have been closed down because of security concerns, affecting 300,000 students in 11 provinces.
A spokesman for Afghanistan's intelligence agency said the Taliban was trying to make families afraid to send their children to school ahead of the scheduled 2014 withdrawal of international combat troops.
The Taliban has not claimed responsibility for the school attacks, but they have carried out violent raids in Takhar Province.
When in power from 1996 to 2001, the Taliban regime banned education for girls. Since having been driven from power, Taliban fighters and their sympathizers have carried out numerous attacks against schools.
In addition to poisonings, they have targeted schools with rockets and mortars, have burned them down, and have thrown acid in the faces of schoolgirls. There have also been reports of Taliban fighters beheading teachers who work at schools for girls.
The UN Afghanistan Assistance Mission (UNAMA) earlier this month condemned the attacks as a violation of the right of Afghan children to be educated.
UNAMA called on the Afghan government and the NATO-led international coalition to "ensure that effective security measures are in place to protect schools, students, and teachers."
With reporting by Reuters and dpa