The Hermann AVA is located in Gasconade County, and entirely contained within the larger Ozark Mountain AVA. The wine appellation is located on the southern side of the Missouri River near the town of Hermann, about halfway between St. Louis and Jefferson City. The AVA covers the northernmost hills of the Ozark Plateau with many of the 200 acres (80 hectares) of vineyards planted along hillside locations. The area is a flood plain with alluvial soil deposits up to 30 feet (9 m) deep. Growing conditions in the area have been compared to those in southern and eastern Germany.

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