It was headed by a Grand Inquisitor, or General Inquisitor, named by the Pope but selected by the king, always from within the royal family.

The Grand Inquisitor would later nominate other inquisitors. Diogo da Silva, personal confessor of King John III and Bishop of Ceuta.

He was followed by Cardinal Henry, brother of John III, who would later become king. Like the Spanish Inquisition, it concentrated its efforts on rooting out those who had converted from other faiths (overwhelmingly Judaism) but did not adhere to the strictures of Catholic orthodoxy.

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The Portuguese Inquisition (Portuguese: Inquisição Portuguesa) was formally established in Portugal in 1536 at the request of its king, John III.

Under John III, the activity of the courts was extended to the censure of books, as well as undertaking cases of divination, witchcraft and bigamy.

Originally aimed at religious matters, the Inquisition had an influence on almost every aspect of Portuguese life — political, cultural, and social.

In Portuguese India, the Goa Inquisition also turned its attention to Indian converts from Hinduism or Islam who were thought to have returned to their original ways.

Manuel I had asked for the installation of the Inquisition in 1515 to fulfill the commitment of marriage with Maria of Aragon, but it was only after his death that Pope Paul III acquiesced.

In the period after the Medieval Inquisition, it was one of three different manifestations of the wider Christian Inquisition along with the Spanish Inquisition and Roman Inquisition.