Egyptian Coptic Christian Pope Shenouda III, the patriarch of most of Egypt's estimated 12 million Christians, died on Saturday from old age, his political adviser told Reuters.
Bells tolled in Cairo's Abbasiya district, site of Egypt's main Coptic cathedral, as the news spread.
Shenouda, 88, became the 117th Pope of Alexandria in November 1971, and was popular among Egypt's Christians and Muslims alike during his four decades in power.
His successor will play a central role in forging the church's position in the country after the overthrow of president Hosni Mubarak last year. Islamist parties have since swept parliamentary elections and will dominate the debate over drawing up the country's new constitution.
He died from complications in health and from old age, adviser Hany Aziz said. Shenouda had recently returned from abroad where he had been seeking medical treatment.
Shenouda's criticism of the government's handling of an Islamic insurgency in the 1970s, in which Christians were targets, and his rejection of Egypt's 1979 peace treaty with Israel landed him in trouble with then-president Anwar Sadat.
Sadat banished him to the Wadi el Natrun monastery north west of Cairo and stripped him of his temporal powers.
Under more than a quarter century of President Mubarak's rule, relations between the government and the Coptic church were generally smooth, with the Pope portrayed in state media as a symbol of religious harmony, despite occasional outbreaks of sectarian violence.
On Saturday, condolences poured in from Egypt's Muslim leaders and from politicians.
Egypt has lost one of its rare men at a sensitive moment when it most needs the wisest of its wise - their expertise and their purity of minds, said Sheikh Ahmed el-Tayib, grand imam of Egypt's highest Islamic authority, al-Azhar.
He held the question of Jerusalem and the Palestinian problem in his conscious, the state Middle East news agency quoted him as saying.
Mohamed Mursi, chairman of the Muslim Brotherhood's Freedom and Justice Party (FJP), said Pope Shenouda had a long journey of service during the nation's history.
The Freedom and Justice Party sends its deepest condolences to the Egyptian people and our Christian brothers over the death of Pope Shenouda III, he said in statement on the website of the FJP, which took almost half the seats in Egypt's new parliament.
Father Anglos Ishaq, head of the church on Egypt's north coast, said a temporary replacement would be chosen until a new pope was elected.
It is too early to know what will happen next, but what is known is that the oldest bishop in the Holy See will be chosen as charge d'affaires until a new pope gets chosen by elections from different church councils in the different provinces.
He said the pope's body was expected to remain in a coffin for three days, provided doctors gave their approval.
All details about the burial and how long his body will remain for people to come and receive blessings will be decided by doctors, Father Anglos said. But surely people will get some time to see the body and receive blessings.
A Vatican spokesman said Pope Benedict was immediately informed of Shenouda's death and offered prayers for him. The Catholic Church joins Christians in their pain and prayer over the death ... of their spiritual leader, he said.
(Reporting by Yasmine Saleh and Dina Zayed; Writing by Patrick Werr; Editing by Andrew Heavens)