We investigated the efficacy of discriminating fish acute toxicity syndromes (FATS) on the basis of literature sources of fish physiological responses exposed to four xenobiotic chemicals. The following FATS were included in a discriminant function model: nonpolar narcosis, acetylcholinesterase (AChE) inhibition, oxidative phosphorylation uncoupling, and respiratory membrane irritation. Two xenobiotics, chlorine and zinc sulfate, were suspected of eliciting a toxic syndrome already known to the model, while the other two, rotenone and cyanide, were presumed to elicit a response syndrome unknown to the model. The model correctly discriminated the toxic responses for fish exposed to chlorine and zinc sulfate into the respiratory irritant syndrome, while classifications of fish exposed to rotenone and cyanide were conflicting and suggested a new FATS would be required. We then identified a respiratory blocker syndrome for fish exposed to rotenone and cyanide, and the model discriminated well between these five FATS groups. Moreover, to evaluate disparities between the exposure system used to develop the four original FATS model and the literature values, we tested rotenone with our exposure system and experimental design. Three of four rotenone-exposed fish were discriminated from the original four FATS, yet results observed were slightly different for rotenone-exposed fish in comparison with rotenone values from the literature. The reasons for these discrepancies were due to the lack of inclusion of several important discriminating variables from literature sources, differences in exposure, and because different species were used in the rotenone exposures. Yet, despite these differences these data suggest that literature sources can be used in a quantitative fashion to improve our understanding of mechanisms associated with toxicity.