Many contaminants are chiral compounds with enantiomers that may differ markedly in environmental fate, bioavailability, and toxicity. Enantiospecific environmental fate and ecotoxicological information are lacking for many chiral contaminants. The primary objective of this investigation included an assessment of potential enantiospecific differences in sublethal standardized and behavioral responses of the model organisms Pimephales promelas (teleost) and Daphnia magna (crustacean) to the widely prescribed chiral antidepressant fluoxetine. Endpoints assessed included D. magna immobilization, reproduction, and grazing rate and P. promelas survival, growth, and feeding rate. S-Fluoxetine was found to be more toxic to sublethal standardized and behavioral endpoints in P. promelas, potentially because its primary active metabolite, S-norfluoxetine, is more potent than the same metabolite of R-fluoxetine in mammals. This was not observed for D. magna responses. This differential enantiospecific response between model organisms may have resulted from closer target homology between mammals and fish than between mammals and crustaceans. P. promelas feeding rate, an ecologically relevant and mode-of-action related response, was the most sensitive endpoint tested for R- and S-fluoxetine with 10% effect concentration (EC10) values (+/-SE) of 16.1 (+/-20.2) and 3.7 (+/-4.6) microg l(-1), respectively. Up to a 9.4-fold difference in toxicity between enantiomers was observed; P. promelas growth EC10s (+/-SE) for R- and S-fluoxetine were 132.9 (+/-21.2) and 14.1 (+/-8.1) microg l(-1), respectively. Such differences in sublethal responses to fluoxetine enantiomers suggest that enantiospecific toxicity and mode-of-action related responses that are ecologically relevant (e.g., feeding rate) should be considered in future ecological hazard and risk assessments for chiral contaminants.