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Highway 221 is a mostly north-south highway in north central Arkansas. Its northern terminus is at the Missouri state line, where it continues as Route 39. Highway 221 continues south approximately 8 miles before intersecting Highway 21, where the two routes run concurrent approximately 2 1/2 miles to U.S. Route 62 at Berryville, where 21 and 221 split. 221 runs concurrent with US 62 west for approximately 1/4 mile, then turns south and runs approximately 11 miles before ending at the Madison / Carroll County line, where it continues as Rockhouse Road.
