The physiological responses of Myriophyllum spicatum to 2,4-D, diquat and copper were quantified using a plant tissue viability assay, and daily measures of dissolved oxygen and pH. Correlations of herbicide tissue residues to physiological response measures were determined and the relationship was used to develop exposure-response models. Diquat and copper had a greater effect on plant tissue viability than was observed for 2,4-D. Diquat produced greater reductions in dissolved oxygen concentrations and pH values than 2,4-D or copper. Copper exposure had the least effect on these parameters. Exposure-response models developed for 2,4-D predicted effective control at plant tissue residues ranging from 4000 to 4700 mg/kg. Aqueous exposure concentrations necessary to produce effective control plant tissue residues ranged from 0.20 to 0.40 mg/L. Exposure-response models developed for diquat predicted effective control at plant tissue residues ranging from 225 to 280 mg/kg. Aqueous exposure concentrations necessary to produce effective control plant tissue residues ranged from 0.113 to 0.169 mg/L. Exposure-response models developed for copper predicted effective control at plant tissue residues ranging from 680 to 790 mg/kg. Aqueous exposure concentrations necessary to produce effective control plant tissue residues ranged from 0.32 to 0.64 mg/L. Model predictions for 2,4-D, diquat and copper were within 0.5 mg/L of the manufacturers' label recommendations for these herbicides. The use of laboratory microcosms in development of exposure-response models for diquat and copper produced results comparable to those using the larger-scale greenhouse systems. Diquat effectively controlled M. spicatum at lower tissue residues than 2,4-D or copper. In addition, initial aqueous exposure concentrations were also lower for diquat. Use of these models in field situations should be coupled with considerations of quantity of biomass present and environmental conditions, such as turbidity, in order to accurately calculate exposure concentrations necessary for effective tissue residues. Thus, the use of these models can be used to optimize the impact on the target species while minimizing exposure for nontarget species.