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John Wesley Powell, in the nineteenth century, introduced the notion that the 100th meridian divides the North American continent into arid western regions and humid eastern regions. This concept remains firmly fixed in the national imagination. It is reexamined in terms of climate, hydrology, vegetation, land use, settlement, and the agricultural economy. It is shown there is a stark east-west gradient in aridity roughly at the 100th meridian that is well expressed in hydroclimate, soil moisture, and "potential vegetation.’’ The gradient arises from atmospheric circulations and moisture transports. In winter, the arid regions west of the 100th meridian are shielded from Pacific storm-related precipitation and are too far west to benefit from Atlantic storms. In summer, the southerly flow on the western flank of the North Atlantic subtropical high has a westerly component over the western plains, bringing air from the interior southwest, but it also brings air from the Gulf of Mexico over the eastern plains, generating a west-east moisture transport and precipitation gradient. The aridity gradient is realized in soil moisture and a west-to-east transition from shortgrass to tallgrass prairie. The gradient is sharp in terms of greater fractional coverage of developed land east of the 100th meridian than to the west. Farms are fewer but larger west of the meridian, reflective of lower land productivity. Wheat and corn cultivation preferentially occur west and east of the 100th meridian, respectively. The 100th meridian is a very real arid-humid divide in the physical climate and landscape, and this has exerted a powerful influence on human settlement and agricultural development.