At that time, a huge part of the present-day rione was gloomy and infamous, as it housed the Campus Sceleratus, a large area just outside Porta Collina (between Via Venti Settembre and Piazza dell'Indipendenza) where Vestal virgins who infringed their chastity vows were buried alive.

The refurbishments promoted by Sixtus V also involved the intersection between Via Sistina and Via Pia, where the Quattro Fontane were positioned, thus creating a scenic viewpoint where people used to stop in summertime and enjoy "the good air", which is unimaginable today.

It must be said that Cardinal Peretti had shown his great interest in this area even before he became Pope, as he ordered the construction of a huge villa, with a park richly adorned with fountains and portals, between Santa Maria Maggiore and the present Via Marsala and Via del Viminale.

After the Capture of Rome, the rione experienced a feverish development, just as the other rioni that were urbanized at the time, and a number of huge stile umbertino palaces, such as the headquarters of the Ministers of Treasury and of Defence, were built alongside Via Venti Settembre; relevant arteries were also opened, such as Via Nazionale and Via Cavour.

Southward, Castro Pretorio borders with Esquilino (R. XV), whose boundary is outlined by Piazzale Sisto V, Via Marsala, Viale Enrico De Nicola, Piazza dei Cinquecento, Via Giovanni Giolitti and Via Gioberti.

This is the most populated area of the rione, showing the urban coexistence of two-storey villas, stile umbertino palaces, offices and more or less luxurious hotels intended to accommodate the large number of tourists from the nearby Termini railway station.