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In his homily at New Year's Day mass, the pope spoke of mounting tensions, "especially discrimination, abuse and religious intolerance which are today striking Christians in particular."
"I once again launch a pressing appeal not to give in to discouragement and resignation," he said, calling for the "concrete and constant engagement of leaders of nations" to protect Christians.
The Latin Patriarch of Jerusalem Fuad Twal called on Christians to show courage in the face of the attack.
"This latest massacre must lead us to reflect on our vocation as Christians in this region, which cannot be allowed to turn its back on the Cross," said Twal, the highest Roman Catholic prelate in the Holy Land.
Condemnation and condolences also flowed out from across the Middle East.
Saudi Arabia strongly "condemns this criminal act which neither our religion nor international norms and ethics approve of," said a foreign ministry official on state news agency SPA. It described the attack as "terrorist".
The head of the Organisation of the Islamic Conference, Ekmeleddin Ihsanoglu, "condemned in the strongest terms the criminal and terrorist act".
He urged Egyptians "to disassociate themselves from attempts to instigate sedition or spread division among the people which some want to implant among them".
In Damascus an official said, "Syria strongly denounces this terrorist crime, which is targeting the national unity and religious pluralism of Egypt and other Arab countries."
The Islamist Palestinian movement Hamas also condemned the attack, saying it was "certain it was the work of elements acting against the interests of Egypt and looking to promote confrontation between Muslims and Christians".
A top Shiite Muslim leader in Lebanon, Sheikh Abdel Amir Kabalan, denounced the attack as a "terrorist act aimed at sowing chaos and fear in Egypt".
"This terrorist act bears the fingerprints of Zionists who keep on targeting religious sights and are working to ... sow discord between Muslims and Christians," Kabalan said in a statement.
King Mohammed VI of Morocco said in a letter to Egyptian President Hosni Mubarak the attack was a "crime against all of humanity" which "is banned by the values of Islam".
"This abject criminal act is contrary to the peaceful nature of the Egyptian people and the history of one of the oldest civilisations with its true traditions of tolerance and cohabitation between religions and cultures."
US President Barack Obama denounced the bombing as "outrageous".
"The perpetrators of this attack were clearly targeting Christian worshippers, and have no respect for human life and dignity. They must be brought to justice for this barbaric and heinous act," Obama stressed.
The EU's foreign affairs chief Catherine Ashton said in a statement there could be no justification for the attack.
"The right of Christian Copts to gather and worship freely must be protected," she said.
French President Nicolas Sarkozy condemned the blast as cowardly and barbaric, in a letter of condolence to his Egyptian counterpart.
"It is with concern and great emotion that I learned of the terrorist attack which cost the lives of more than 20 people and wounded close to 100," Sarkozy wrote to Mubarak.
"Nobody should be worried nor afraid for their life in exercising their fundamental right to freely practise their faith," Sarkozy wrote.
"Facing terrorism and extremism ... France will always be at your side," he said.
Alistair Burt, a junior British foreign minister, said Britain sent "sincere condolences".
"At the start of a new year the world must be increasingly vigilant against such attacks wherever they occur, remain united in promotion of common values of tolerance and stand against the terrorist philosophy of violence," he said.
Italy's foreign ministry denounced "the dramatic and systemic violence and persecution that Christian communities have for too long been submitted to in various parts of the world."
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"I once again launch a pressing appeal not to give in to discouragement and resignation," he said, calling for the "concrete and constant engagement of leaders of nations" to protect Christians.
The Latin Patriarch of Jerusalem Fuad Twal called on Christians to show courage in the face of the attack.
"This latest massacre must lead us to reflect on our vocation as Christians in this region, which cannot be allowed to turn its back on the Cross," said Twal, the highest Roman Catholic prelate in the Holy Land.
Condemnation and condolences also flowed out from across the Middle East.
Saudi Arabia strongly "condemns this criminal act which neither our religion nor international norms and ethics approve of," said a foreign ministry official on state news agency SPA. It described the attack as "terrorist".
The head of the Organisation of the Islamic Conference, Ekmeleddin Ihsanoglu, "condemned in the strongest terms the criminal and terrorist act".
He urged Egyptians "to disassociate themselves from attempts to instigate sedition or spread division among the people which some want to implant among them".
In Damascus an official said, "Syria strongly denounces this terrorist crime, which is targeting the national unity and religious pluralism of Egypt and other Arab countries."
The Islamist Palestinian movement Hamas also condemned the attack, saying it was "certain it was the work of elements acting against the interests of Egypt and looking to promote confrontation between Muslims and Christians".
A top Shiite Muslim leader in Lebanon, Sheikh Abdel Amir Kabalan, denounced the attack as a "terrorist act aimed at sowing chaos and fear in Egypt".
"This terrorist act bears the fingerprints of Zionists who keep on targeting religious sights and are working to ... sow discord between Muslims and Christians," Kabalan said in a statement.
King Mohammed VI of Morocco said in a letter to Egyptian President Hosni Mubarak the attack was a "crime against all of humanity" which "is banned by the values of Islam".
"This abject criminal act is contrary to the peaceful nature of the Egyptian people and the history of one of the oldest civilisations with its true traditions of tolerance and cohabitation between religions and cultures."
US President Barack Obama denounced the bombing as "outrageous".
"The perpetrators of this attack were clearly targeting Christian worshippers, and have no respect for human life and dignity. They must be brought to justice for this barbaric and heinous act," Obama stressed.
The EU's foreign affairs chief Catherine Ashton said in a statement there could be no justification for the attack.
"The right of Christian Copts to gather and worship freely must be protected," she said.
French President Nicolas Sarkozy condemned the blast as cowardly and barbaric, in a letter of condolence to his Egyptian counterpart.
"It is with concern and great emotion that I learned of the terrorist attack which cost the lives of more than 20 people and wounded close to 100," Sarkozy wrote to Mubarak.
"Nobody should be worried nor afraid for their life in exercising their fundamental right to freely practise their faith," Sarkozy wrote.
"Facing terrorism and extremism ... France will always be at your side," he said.
Alistair Burt, a junior British foreign minister, said Britain sent "sincere condolences".
"At the start of a new year the world must be increasingly vigilant against such attacks wherever they occur, remain united in promotion of common values of tolerance and stand against the terrorist philosophy of violence," he said.
Italy's foreign ministry denounced "the dramatic and systemic violence and persecution that Christian communities have for too long been submitted to in various parts of the world."
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