Masked gunmen attacked a bus carrying Coptic Christians on a visit to a monastery south of the Egyptian capital on Friday, killing at least 26 people, officials said.
The assailants sprayed the bus headed for Saint Samuel monastery in Minya province with gunfire before fleeing, provincial governor Essam el-Bedawi told state television.
"They used automatic weapons," he said.
Health ministry spokesman Khaled Megahed told state television that 26 people were killed and another 25 wounded.
Bedawi said police were fanning out along the road where the attack took place and had set up checkpoints.
The shooting followed church bombings in December and April claimed by the Islamic State (IS) jihadist group that killed dozens of Copts.
The jihadists threatened more attacks against the Copts, who make up about 10 percent of Egypt's 90-million population.
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.
Egypt says it has identified those behind the church bombings, 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.
However, rights groups accuse the former army chief of crushing even peaceful opposition to his rule.
A pro-state daily, Al-Bawaba, said on its website that an edition critical of security provisions after the church bombings had been banned from publication.