The efforts of Charles to enforce his family's pretensions to the Countship of Provence, and his temporary assumption, with this object, of the title of Cardinal of Anjou were without success.

He coquetted for instance on the one hand with the Lutheran princes of Germany, and on the other his interview (1558) with the Cardinal de Granvelle (at Péronne) initiated friendly relations between the Guises and the royal house of Spain.

He was instructed to arrive at an understanding with the Germans, who proposed to reform the church in head and members and to authorize at once Communion under Both Kinds, prayers in the vernacular and the marriage of the clergy.

However, in September 1563, on a visit to Rome, the cardinal, intent perhaps on securing the pope's assistance for the political ambitions of the Guises, professed opinions less decidedly Gallican.

In 1570, he aroused the anger of Charles IX by inducing Duke Henri, the eldest of his nephews, to solicit the hand of Margaret of Valois, the king's sister.

His share in the negotiations for the marriage between Charles IX and Elizabeth of Austria, and for that of Margaret of Valois with the prince of Navarre, granted him temporary favour.

One of them, "La Guerre Cardinale" (1565), accuses him of seeking to restore to the Holy Roman Empire the three former prince-bishoprics of Metz, Toul and Verdun, in Lorraine, which had been conquered by Henry II.