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The term inquisition can refer to either an investigation by the Roman Catholic Church into heresy, or to the department appointed to perform such investigations. This is currently titled the Congregation for the Doctrine of the Faith since 1965, but was formerly been titled the Supreme Sacred Congregation of the Holy Office, and prior to that the Supreme Sacred Congregation of the Roman and Universal Inquisition. Several major inquisitions took place, under the management of differing departments.

Many of these inquisitions are known to have used brutal torture to extract confessions from accused heretics. While many of these accused heretics would be allowed free after repenting their views and stating their loyalty to the Church, a significant number - consisting almost entirely of those who refused to repent - were executed by a variety of deliberately painful methods including burning at the stake while alive, boiling in oil and the 'breaking wheel.'

Execution was never carried out by the church directly for theological reasons, but by secular authorities. This procedure was clarified in the Ad exstirpanda papal bull written by Pope Innocent IV in 1252, which also authorized the use of torture for extracting confessions from the accused and recommended burning at the stake as the appropriate punishment for those found guilty and unrepentant. Ad exstirpanda marked the beginning of one of the most brutal periods of Inquisition.

The sufferings and martyrdoms of Protestants are recounted in Foxe's Book of Martyrs. The persecutions of Anabaptists and other radical dissenters from earlier centuries is chronicled in the more extensive work, Martyr's Mirror.

The best known of the four major inquisitions was the Spanish Inquisition, which ran from 1438 onwards. One of its primary tasks was enforcement of the Alhambra Decree by the monarchs of Spain in 1492, ordering the immediate expulsion of all Jews from the country and its territories.

The Office of the Inquisition would not be established until 1542 by Pope Paul III, with its stated objective "to maintain and defend the integrity of the faith and to examine and proscribe errors and false doctrines.'