As Prior General he was particularly vigilant in attempting to halt any further effect of Lutheranism upon members of the Order.
At the General Chapter in 1539 when he began his term as Prior General, he had three new regulations enacted.
By one of these regulations, he withdrew the right to preach from all Augustinians in Italy, until they established their orthodoxy to his satisfaction.
At the next General Chapter in 1543, he enacted that any Augustinian about whom grave theological doubt arose was "no longer to be received in any (Augustinian) monastery."
Because of the regard of the Pope and of Italian eccleasiastical authorities for Seripando, in 1542 he was granted permission to examine on behalf of the Church any Augustinians accused of incorrect teaching.
It was felt that his adjudication would not be any more lenient that would be that of Church authorities.
He used both his strictness and his fatherly concern as necessary, defending some Augustinians fallsely accused and persuading others to ammend their preaching before it definitely crossed over into non-Catholic doctrine.
Council of Trent, 1546 - 1563.
As Prior General, he attended in 1546 the sessions of the Council of Trent, where he distinguished himself by his scholarly involvement, and particularly by his views on the theology of justification.
Pope Paul III sent him as his legate to the emperor and to the King of France, after which mission he was offered the Bishopric of Aquila.
Seripando not only declined this offer, but also resigned as Prior General in 1551. He resigned because he was physically drained and in failing health, even though only fifty years old. He withdrew into a small convent (convento).
From this retirement he was called in 1553 on a mission from the city of Naples to Emperor Charles V.
Upon completion of that task, he was appointed Archbishop of Salerno by Emperor Charles V in 1553, and was a zealous and efficient pastor.
His brief time as an archbishop, which spanned the years 1554 to 1563, has received little attention among scholars compared to the work that has been done on his efforts as Prior General and later as a legate of the pope at the Council of Trent.
Yet, his years as bishop deserve special attention. Girolamo Seripando believed that the office of bishop needed to be restored if a general reform of the Church, clergy, and the faithful were to be accomplished.
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