A Fish Botulism Exposure Model was developed to compare the sensitivity of rainbow trout, round goby, walleye and yellow perch to botulinum neurotoxin type E (BoNT/E) at three treatments; 800, 1,500 and 4,000 Mouse Lethal Doses. Comparisons revealed that significant variability exists in clinical signs and mortality patterns between the four species. Each species expressed unique clinical signs consisting of changes in both behaviour and skin pigmentation prior to death. Yellow perch lived significantly longer (p < 0.05) than the three other species at all treatments. Post mortem analysis of experimental fish demonstrated that BoNT/E was present in both the fillet musculature and non-fillet samples of some species. Results of this study suggest that live fish can represent a significant vector for transfer of BoNT/E to birds that eat live fish, but human health risks associated with the consumption of these species during botulism epizootics are minimal.