Isotopic analyses of Eocene sandstones from the Tyee Formation and related units in the U.S. Pacific Northwest provide evidence for short residence time but extensive mixing and, indirectly, slow subsidence rates within the major river feeder systems that drained the western flank of the North American Cordillera. Bulk isotopic analyses of coarse white mica are remarkably consistent throughout the Tyee Formation (mean K/Ar = 67.3 Ma, δ18O ≈+9.5) of the Oregon Coast Range. Other Tertiary sandstones in the region have similar values. Despite small scatter about these mean values, the 40Ar/39Ar ages of single grains of white mica from these units range from about 45 to 120 Ma, showing that long river systems thoroughly mixed and homogenized the transported sand grains. In addition, overlap of the youngest mica cooling ages and depositional age for the Tyee Formation show that homogenization of grains took place during a relatively short residence time in the river transport system (<2 m.y.). These results require that the sediments were multiply cycled within the active river system. This suggests that average subsidence rates along the alluvial system were low, and thus sediment could be recycled by temporary storage in, and reintroduction from, the river flood plain without spending significant time buried. The results show that extensive sediment mixing can occur in large rivers on relatively short time scales, and that isotopic analyses can provide indirect evidence of subsidence rates for basins no longer preserved.