This study provides an assessment of the ecological conditions of a 46-km effluent-dominated stream section of the Santa Cruz River in the vicinity of the International Waste Water Treatment Plant, Nogales, AZ. We associated changes in the structure of the macroinvertebrate community to natural and anthropogenic chemical and physical variables using multivariate analysis. The analysis shows that biological criteria for effluent-dominated streams can be established using macroinvertebrate community attributes only with an understanding of the contribution of three classes of variables on the community structure: (1) low flow hydrological discharge as affected by groundwater withdrawals, treatment plant discharge, and subsurface geomorphology; (2) chemical composition of the treatment plant discharge and natural dilution; and (3) naturally produced floods resulting from seasonality of precipitation. ?? 2003 Elsevier Science Ltd. All rights reserved.