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This region borders with Illinois to the west across the Mississippi River. It is characterized by rich farmlands, part of the Till Plains. Interstate 70 stretches across in a northeast/southwest direction and I64 travels southeast/northwest. West from Ellis Grove, Bluff Road offers views of lofty limestone bluffs on one side and the expanse of the American Bottoms - original Mississippi riverbed. From Ellis Grove to Prairie Du Rocher and Fort de Chartres State Historic Site, the road is a section of the Great River Road National Scenic Byway.

Monroe County is pocked with more than 100 caves, the state's largest number; Illinois Caverns near Waterloo are accessible by the public.

At Collinsville is the Cahokia Mounds State Historic Site, consisting of the remains of an ancient city founded by a Mississippian people that flourished from 700 to 1400 A.D., then disappeared. Now listed by UNESCO, it is the only prehistoric Native American city north of Mexico. Monks Mound, also here, is the largest prehistoric earthen mound in the New World. Horseshoe Lake State Park in Granite City comprises an ancient oxbow lake, diverse wetlands and a low flood plain environment. Birders will espy a vast array of species along the Walker Island bird walk. Native American groups evidently inhabited the area, dating to 8,000 B.C.

In Hartford, the Lewis & Clark National Trail Site No. One marks the starting point of their expedition. The Lewis & Clark Heritage Center here recounts the history of Camp DuBois, the party's training grounds and winter camp.

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