We estimate slip rates on major active faults in southern California using a block model constrained by Global Positioning System measurements of interseismic deformation. The block model includes the effects of block rotation and elastic strain accumulation consistent with a simple model of the earthquake cycle. Our estimates of the right-lateral strike-slip rate on the San Andreas fault vary by at least a factor of 5, from a high of 35.9 ± 0.5 mm/yr in the Carrizo Plain to a low of 5.1 ± 1.5 mm/yr through the San Bernadino segment. Shortening across the Puente Hills Thrust and left-lateral slip on the Raymond Hill fault are consistent with both thickening and escape tectonics in the Los Angeles Basin. Discrepancies between geodetic and geologic slip rate estimates along the San Andreas and San Jacinto faults, as well as in the Eastern California Shear Zone, may be explained by a temporal change in fault system behavior. We find no substantial evidence for long-term postseismic relaxation and infer that the viscosity of the lower crust/upper mantle may be relatively high (η > 1019 Pa s).