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On a major road, and also roughly on a straight line, it is Greenville MS.

The exact midpoint is near Eudora, Arkansas (SW across the Mississippi River).

Greenville is on the Mississippi River, but not any interstate highways, so alternatives could be

Shreveport LA (on hwys 20 and 49)

Memphis TN (on hwys 30/40 and 55)

Jackson MS (on hwys 20 and 55).

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10y ago

What else can I help you with?