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In Etruscan and Roman times, the ridge on which Panicale is situated belonged to Chiusi. In all probability, the town was originally founded in the 7th or 8th century AD, during the time of the Lombards, as one of Tuscia's fortified centres. From the 11th century, Panicale became a strategic centre of particular importance for the territorial domination by Perugia, situated as it is in control of the Nestore Valley and Lake Trasimeno. The inhabited centre, which faces the lake like a natural gallery, developed around 3 squares. The lowest is the ancient square of the municipality, containing the 14th century Magistrate's Palace. From here the road goes to the square of the Collegiate Church of St. Michael the Archangel, the oldest in the area (10th and 11th century).
The street continues uphill until it reaches the square containing the Mayor's Palace. Outside the Fiorentina Gate is the 13th century St. Augustine's Church and the Church of the Madonna della Sbarra, in late 16th century style. Inside the Church of St. Sebastian, dating back to the 14th century, is the "Martyrdom of St. Sebastian" (1505), by Il Perugino, one of the most important frescoes by the Master in Umbria. There are several interesting Sanctuaries in the vicinity. The Sanctuary delle Grondici, about 10 Km from Panicale was built at the end of the 15th century. In the nearby town of Tavernelle, there is the Renaissance Sanctuary of Mongiovino. About 1 Km from Panicale is the Church of St. Maria della Quercianola, consacrated by Pope Paolo III in 1543.
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