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An analysis of the historical relationships of 19 river drainages (St. Lawrence to Altamaha) on the Atlantic slope of the Appalachian Mountains was conducted using the shared presence of 124 native species of cyprinid fishes. This analysis resulted in an area cladogram that suggests that the rivers of the southern Atlantic slope were historically connected to the drainage of three southern rivers (Flint, Chattahoochee, and Apalachicola) which drain into the Gulf of Mexico. The mid Atlantic and northern Atlantic slope rivers appear to be historically related in support of earlier hypotheses that the mid Atlantic region provided a refugium for fishes to disperse to the north following the retreat of the glacier and rising sea levels at the end of the Pleistocene. Methods for testing these conclusions are discussed.