Masked gunmen attacked a bus carrying Coptic Christians on a visit to a monastery south of the Egyptian capital on Friday, killing at least 28 people including children, officials said.
The assailants in three pick-up trucks attacked the bus as it carried visitors to the Saint Samuel monastery in Minya province, more than 200 kilometres (120 miles) from Cairo, before fleeing, the interior ministry said.
It was the latest attack on Copts after Islamic State (IS) group jihadists bombed three churches in December and April, killing dozens of Christians.
Pictures of the bus aired by state television showed the vehicle riddled with machinegun fire and its windows shot out.
Cellphone footage and pictures circulated on Egyptian media sites showed several victims who had apparently been shot dead scattered in the desert sand around the bus.
State television quoted a health ministry official as saying a "large number" of the victims were children.
"They used automatic weapons," Minya governor Essam el-Bedawi told state television of the attackers.
Bedawi said police were fanning out along the road where the attack took place and had set up checkpoints.
State television reported that the attack killed 28 people, citing the health minister.
The latest attack came after jihadists had threatened more strikes against the Copts, who make up about 10 percent of Egypt's 90-million population.
In a statement on its spokesman's Facebook page, the Coptic Church called for "measures to be taken to prevent the dangers of those incidents that tarnish Egypt's image".
Suicide bombers with the jihadist group struck a Cairo church on December 11, next to the seat of the Coptic pope, killing 29 people.
On April 11, bombers attacked two churches north of Cairo on Palm Sunday, killing 45 people, in the deadliest strike in living memory against the Copts.
The Copts' Pope Tawadros II had been leading a service in one of the two churches attacked that day.
The bombings prompted President Abdel Fattah al-Sisi to declare a three-month state of emergency.
The Egyptian affiliate of IS has also killed several Copts in North Sinai, forcing dozens of families to flee the province in January.
Friday's shooting came after a historic visit to Egypt by Roman Catholic Pope Francis to show solidarity with the country's Christians.
In his late April trip, Francis visited one of the bombed Coptic churches and condemned violence carried out in the name of God.
Al-Azhar, Egypt's top religious authority, condemned Friday's shooting which took place on the eve of the start of the Muslim holy month of Ramadan.
"The Minya incident is unacceptable to Muslims and Christians and it targets Egypt's stability," Al-Azhar's Grand Imam Ahmed al-Tayeb said in a statement.
Israel, with whom Egypt signed a peace treaty in 1979, also condemned the attack.
"Israel strongly condemns the severe terrorist attack in Egypt and sends the condolences of the Israeli people to President al-Sisi and the Egyptian people," a statement from Prime Minister Benjamin Netanyahu's office said.
Copts have suffered sectarian attacks for years.
A suicide bomber attacked a church in 2011, and there have been deadly clashes with Muslims, especially in the rural south, following disputes over church construction.
Egypt says it has identified those behind the church bombings in April, saying they were part of an extremist cell based in southern provinces, offering a reward for their capture.
Sisi has defended the performance of his security forces and accused jihadists of trying to divide Egyptian society by attacking vulnerable minorities.