The spiritual heads of Christianity's two largest churches, Roman Catholic and Orthodox, have taken part in a solemn ceremony at the Vatican.
The bones, in white reliquaries, were blessed by the two leaders
Pope John Paul II handed over to Patriarch Bartholomew the relics of two early Christian saints.
They had been kept in St Peter's in Rome for more than 800 years.
The ceremony aimed to give a push to the Pope's reconciliation efforts with Orthodox Christians who separated from Rome almost 1,000 years ago.
Bartholomew I, Patriarch of Constantinople and spiritual leader of some 300 million Orthodox Christians around the world thanked the Pope profusely for the gesture.
The bones of St John Chrysostom and St Gregory - who were bishops of Constantinople (now Istanbul) in the 4th Century AD - were probably brought to Rome by Crusaders when they sacked Constantinople in the Middle Ages.
They have been interred inside St Peter's basilica for hundreds of years.
The two religious leaders blessed the bones before they were carried away on biers by Vatican ushers.
Now, contained in two new gleaming white alabaster reliquaries, the relics will be flown to Istanbul where another ceremony will be held to mark their return.
In remarks reads by an aide, the Pope called it a "blessed occasion to purify our wounded memories" and to "strengthen our path of reconciliation".
The bones will be welcomed to Istanbul with another ceremony
Bartholomew said the return rectified "an anomaly" and "ecclesiastical injustice".
"This brotherly gesture by the church of Ancient Rome confirms that in the church of Christ there are no problems which are insurmountable, when love, justice and peace meet," he said.
Pope John Paul has made reconciliation with the separated Christian churches one of the main themes of his long pontificate, says the BBC's David Willey in Rome.
Relations between the Vatican and the Orthodox churches are still far from cordial after centuries of theological dispute.
But in his declining years, the Pope refuses to slacken his efforts towards reconciliation.
A senior Vatican cardinal admitted at a recent conference of bishops in Rome that enthusiasm among Catholics for full and visible unity among the separated churches of Christendom is on the wane.
Dialogue between Catholics and Anglicans is bogged down over the issue of the ordination of the women in the Anglican Church.
Meanwhile, relations with the Russian Orthodox are still tense, notwithstanding a recent gift by the Pope of an ancient holy icon to the head of the Russian Church in Moscow.
The Russians accuse the Pope of trying to force conversions of Orthodox believers, a charge which the Vatican strenuously denies.
The ailing Pope insisted on making this unique gesture of restoring to their city of origin these saintly relics, but it seems unlikely to warm relations with Orthodox Christians.