In an ideal world, a few overall indicators of hydrologic alteration would adequately describe the degree of hydrologic alteration caused by various forms of river regulation. Currently over 170 hydrologic indicators have been developed to describe different components of flow regimes, including the widely used Indicators of Hydrologic Alteration (IHA) that characterize the impact of river regulation on flow regimes in environmental flow studies. Many of these IHA indicators are intercorrelated, resulting in considerable information redundancy, which could lead to ineffective environmental flow management decisions. The objective of this research is to develop a small set of independent and representative hydrologic indicators that can best characterize hydrologic alteration caused by reservoirs and other forms of river regulation. Two sets of pre- and post-dam streamflow records are used: (1) based on artificial simulations of a wide range of reservoir release rules and (2) streamflow records for 189 gaging stations throughout the United States. Principal component analysis was used to address the intercorrelation among the IHA parameters. Results revealed that the recently introduced metrics termed ecodeficit and ecosurplus can provide a good overall representation of the degree of alteration of a streamflow time series. Across both datasets, 32 individual IHA statistics and several potential generalized indices, three indices based on the ecodeficit and ecosurplus explained the most variability associated with the ensemble of 32 IHA statistics.