While the 79-year-old pope has set closer ties with the Orthodox Church as a priority, the goal has been upstaged during his four-day trip to Turkey by the need to address anger in the Muslim world over his remarks in September seen as linking Islam with violence.
Tight security was in place in Istanbul for what is considered the most volatile part of Benedict's visit, and the route of his motorcade following his arrival in the city of more than 12 million people - where some 15,000 people demonstrated on Sunday against the visit - was kept secret.
"The pope celebrated mass at one of the holiest Christian sites in Turkey amid tight security"
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Two more demonstrations were expected on Thursday, when the pope's programme will take him to two sensitive sites - the Hagia Sophia Museum and the Blue Mosque, the two most prominent Christian and Muslim edifices of Istanbul.
Benedict will be the second pope to visit a mosque after his predecessor John Paul II did so in Damascus, in 2001.
The schism between the Eastern and Western Rites was sealed in 1054 after long-running disputes over papal primacy and theological differences.
In 1204, the Fourth Crusade carried out the brutal sack of Constantinople, modern-day Istanbul, further deepening hostilities.
Benedict is following the lead of his late friend and mentor John Paul II, who visited Istanbul in 1979, just one year after he was elected pope, to announce the creation of a joint Orthodox-Catholic committee to resolve differences.
At a meeting at the Vatican in July 2004, he and Bartholomew I issued a joint declaration for the resumption of Orthodox-Catholic theological talks, suspended in 2000 after a row over the status of Eastern Catholic Churches.
Benedict and Bartholomew I were to meet again early on Thursday when they were to issue a joint declaration.