Effective stress is the primary control on permeability and thus on flow and water loss for two-well hot dry rock systems involving injection and production that have been tested to date. Theoretical relations are derived for the flow between an injector and producer, including the dependence of permeability on effective stress, Four relations for permeability as a function of effective stress are used to match field data for the hot dry rock systems at Rosemanowes Cornwall, and Fenton Hill, New Mexico. The flow and water loss behavior of these systems are well explained by the influence of effective stress on permeability. All four relations for permeability as a function of effective stress are successful in matching the field data, but some have difficulty in determining unique values for elastic and hydrologic parameters.