Although select stream flows in the southwestern United States are dominated by effluent discharges, metal hazards have not been experimentally evaluated in effluent-dominated streams. Lotic mesocosms were designed to assess cadmium effects on multiple levels of biological organization, to determine relevance to regulatory criteria of standard laboratory toxicity tests, and to link laboratory tests to stream responses. Replicate streams were treated with 15 or 143 microg/L Cd during a 10-d study. Streams were sampled on days 0 and 10 for benthic macroinvertebrates, periphyton, and ecosystem metabolism. Concurrent Ceriodaphnia dubia and Pimephales promelas laboratory tests were performed with water from streams. Individual organism, population, and community response variables were affected by 143 microg/L Cd but not by the I5-microg/L treatment level. A biotic ligand model for cadmium predicted a 48-h median effective concentration (EC50) value of 280 microg/L Cd for C. dubia in these effluent-dominated streams: an EC50 value of 38.3 microg/L Cd was estimated for C. dubia in tests performed with reconstituted hard water. Our findings generally support use of the biotic ligand model for establishing site-specific, acute water quality criteria for cadmium. However, future effluent-dominated stream research is required to evaluate relationships between chronic cadmium exposure and organismal and community responses.