The distribution of river channel deposits and provenance studies of late Eocene to modern river systems in the Great Plains adjacent to the Southern Rocky Mountains indicate three major regional drainage patterns. Upper Eocene through lower Miocene river channel deposits in the region derived from the Front Range and Laramie Mountains flowed east to southeast across the Plains. Deep paleovalleys cut into the mountain ranges were subsequently filled by volcaniclastic sediment. Paleovalley in the southern Front Range and adjacent South Park initially drained toward the southeast, but were disrupted by late Eocene to Oligocene volcanism. A major shift in regional stream patterns occur in the middle Miocene. Streams derived from the Front Range flowed to the northeast. Extensive pediments were developed in the mountains, indicating stable local base levels between the mountain ranges and adjacent Great Plains. Gravels prograded outward from the mountain ranges in extensive, overlapping paleovalley fills. Starting approximately 5 Ma and continuing until today, rivers and streams have been eroding older Tertiary deposits both in the plains and the mountains. The modern North Platte drainage was integrated during the middle Pliocene. The timing of the integration of the South Platte drainage is uncertain, but stream patterns south of the Cache la Poudre River and the modern orientations of older Cenozoic surfaces in the Front Range indicate northward tilting of the mountains and adjacent Great Plains. Eastward tilting is also indicated by the modern drainage patterns in the Laramie Mountains. The area affected by the tilting includes all of the Southern Rockies and the Great Plains west of central Nebraska and western Kansas. Latest Cenozoic climatic changes and integration of the modern river systems may have contributed to the late Cenozoic erosion of the region. However, the shifting drainage patterns indicate that broad regional tectonic tilting of the region has been a major factor.