Dona Catharina acted as regent of Portugal until 1562, when she retired and the cardinal Dom Henrique, younger brother of King João III, took her place. While he was head of the government nothing worthy of mention occurred in South-Eastern Africa. It was his intention to station at Mozambique an ecclesiastical administrator, with authority almost equal to that of a bishop, and a bull was obtained from the pope for the purpose. The archbishop of Goa gave his consent to the separation from his diocese of the territory from the Cape of Good Hope to Melinde. The licentiate Manuel Coutinho, one of the royal chaplains, received the appointment, with a salary of about £80 a year from the 1st of April 1563. But something occurred to prevent the plan being carried into execution, and it was not revived until half a century later.

In 1568 Dom Sebastião, though only in his fifteenth year, was declared to be of age, and was crowned king of Portugal, then an absolute monarchy. His was a strange character: gloomy, but adventurous to the last degree, deeply religious according to the standard of his time, but wilful and vain, brave as any warrior who ever held lance in hand, but rash as the most imprudent of those crusaders whom in many respects he greatly resembled. He had hardly assumed the reins of government when be resolved to create a vast dominion in Africa south of the Zambesi, a dominion which in wealth and importance would rival that of Castile in the countries subjected to that crown by the daring of Cortes and Pizarro.