When Gregorios Palamas defended Hesychasm (the Eastern Orthodox Church's mystical teaching on prayer), Barlaam accused him of heresy.

[4][5][6] Bernardo moved to Constantinople in the 1320s, where he soon gained entrance into ecclesiastical and political circles, especially those around the emperor Andronicus III Palaeologus, who gave him a teaching position at the university.

[6] However, according to Wells, "this formidable learning was coupled with an arrogant, sarcastic manner, so caustic at times that he put off even friends and allies.

Emperor Andronicus III sent Barlaam on important diplomatic missions to Robert the Wise in Naples and to Philip VI in Paris.

In 1339, he was sent to the exiled Pope Benedict XII at Avignon to suggest a crusade against the Turks and to discuss the union of churches, but he was not successful in this endeavour.

Around 1336, Gregory Palamas received copies of treatises written by Barlaam against the Latins, condemning their insertion of the Filioque into the Nicene Creed.

In his response titled "Apodictic Treatises", Palamas insisted that it was indeed demonstrable that the Holy Spirit proceeded from the Father but not from the Son.

In his anti-hesychastic works Barlaam held that knowledge of worldly wisdom was necessary for the perfection of the monks and denied the possibility of the vision of the divine life.

He had shown that, in the hands of monks who were inadequately instructed and ignorant of the true Hesychast teaching, the psycho-physical precepts of Hesychasm could produce "dangerous and ridiculous results".

[10] In response to Barlaam's attacks, Palamas wrote nine treatises entitled "Triads For The Defense of Those Who Practice Sacred Quietude".

It was maintained by the Hesychasts to be of divine origin and to be identical to the light which had been manifested to Jesus' disciples on Mount Tabor at the Transfiguration.

[13] Barlaam viewed this doctrine of "uncreated light" to be polytheistic because as it postulated two eternal substances, a visible and an invisible God.

[15] Barlaam derisively called the Hesychasts omphalopsychoi (men with their souls in their navels) and accused them of the heresy of Messalianism, also known as Bogomilism in the East.

Although Barlaam initially hoped for a second chance to present his case against Palamas, he soon realised the futility of pursuing his cause, and left for Calabria where he converted to the Latin Church and was appointed Bishop of Gerace.

The Zealots of Thessalonica were influenced by Barlaam's teachings, and his arguments affected the dogmatic definition of Hesychasm in the Eastern Church.

Being a humanist, Barlaam placed emphasis on created means of salvation (e.g., philosophy and knowledge) and reduced the role of the grace of the Holy Spirit.