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Nepi is located on a vast tuff promontory surrounded by two deep gorges created by the Puzzolo and Falisco streams. Many artefacts were found dating from the Falisci of the seventh century. Legend has it that the town was founded 548 years before Rome (founded in 753 BC) by the hero Termo Larte.

Its name may derive from Nepa, which in Etruscan means water and Nepi is characterized by water and for being the city of the baths of the Gracchi.

In the Falisco period, in the fifth century BC, the city was surrounded by thick walls described by the historian Livy, and was conquered by the Romans in 383 BC under Furio Camillo. It became a municipality due to its important strategic position along the Via Armerina.

In the sixth century AD it was devastated by Alboin, King of the Lombards, and in 1061 was conquered by Robert Guiscard and later belonged to Matilda of Canossa.

In 1131 it became a free city but it was always at the center of the continuous struggles between the aristocratic families who were contending for the government: the Prefects of Vico, the Anguillara, the Orsini and the Colonna, then, finally, the Borgias and the Farnese. With Borgia, Nepi was fortified with walls and re-used in part those of ancient Faliscan.

With Farnese it had a period of splendour and in 1537 Pope Paul III created a duchy with Castro. In 1545, however, it was transferred to the Apostolic Chamber in exchange for Parma and Piacenza.

Nepi remained under the rule of the Holy See until the proclamation of the Kingdom of Italy.

In 1798 Nepi fought the French troops and the Bourbon troops and there were hundreds of deaths. In the war the Cathedral and the Episcopal Archive were irreparably destroyed.

During the nineteenth century, Nepi was part of the Grand Tour in Italy of famous people and many artists who wanted to learn about this country. Nepi is in the paintings of William Turner and Camille Corot.