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It was founded in 312 BC as a colony of Latins in an area perhaps already housing Volscan settlements, on the route of the Via Latina. It was situated at the confluence of the Liri and Rio Spalla Bassa rivers, whence the name "Interamna" (meaning "between river").
It was a military base during the Samnite Wars, who destroyed it in 294 BC. It was again ravaged by Hannibal in 212 BC; since it later sided for him, after the Carthaginian defeat it was forced by Rome to pay heavy tributes. It became a municipium in 90 BC.
Archaeological remains include numerous inscriptions and few remains of buildings.