In 451, a decisive ecumenical council took place in Chalcedon, a suburb of Constantinople. The resulting statement—which defined Christ as being one "person" with two "natures," divine and human—caused deep and permanent rifts in the worldwide Christian church. The debates over the word "nature" estranged Western Christians from Monophysite ("one nature") Christian groups in Egypt, Syria, and Palestine and split Eastern Christians into those who followed Chalcedon and those who did not.

In 516, Patriarch Elias of Jerusalem called on the monastic leader Sabas to join him in endorsing the council's decision. Sabas gathered 10,000 monks (almost half of the desert population at the time!) in the Holy City, where they and the people of Jerusalem shouted their anathema of those who promoted heresy and division. Cyril of Scythopolis recorded that the commander of the army in Jerusalem fled to Caesarea "in fear of the multitude of monks."

In the past, historians have tended to emphasize the role of bishops and councils in determining Christian doctrine, but in more recent years they have learned not to underestimate the role of the people—including monks. Sabas's monastic protest and the subsequent letter he and his fellow monks wrote to the Monophysite emperor shows how seriously the monks of the Holy Land took their responsibility to uphold orthodoxy. Jerusalem, they believed, was "the eye and light of all the world."

But the monks of Palestine were not always so aggressive in their theological debates. An anecdote from the life of Isaiah of Scetis (ca. 489) reveals the openness and generosity of monastics in the region. When two monks approached the renowned Monophysite elder to ask whether they should keep holding to the Chalcedonian doctrine of Christ, Isaiah's closest disciple Peter conveyed the answer: "The old man says there is no harm in your church; you are well as you are and as you believe." (Peter himself did not share the views of his elder, hastening to add his own commentary: "The old man lives in heaven and does not know the ills done in the council!")

Isaiah's ecumenical sensitivity gained the respect of Chalcedonians and Monophysites alike in the centuries that followed. In fact, his Chalcedonian successors, Barsanuphius and John, were never explicit about their personal doctrinal convictions, refusing to take sides in a battle over "idle words" and discouraging their disciples from condemning their opponents.