In the 13th century, Castiglione became an independent comune. Meanwhile, the river Ombrone had started silting up Lake Prile, which soon became a lagoon. In this newformed lagoon, malaria mosquitoes took hold, weakening the population of Castiglione. The city requested protection from various powers (Siena, the Medici, Aragon) and finally became part of the Grand Dukedom of Tuscany under the dynasty of Lorraine.
