Pope Gregory XV (1621–23) sent him as nuncio to the court of Naples. Urban VIII sent him to accompany his nephew, Francesco Barberini, whom he had accredited as nuncio, first in France and then in Spain, where Pamphilj had the firsthand opportunities of forming an intense animosity towards Barberini. In reward of his labors, Giovanni Battista was made apostolic nuncio at the court of Philip IV of Spain (1621–65).