The environmental fate, persistence, and point-source discharge of traditional molluscicidal compounds led to the development of an alternative biomolluscicide, Zequanox. Previous studies evaluated the efficacy and non-target animal safety of Zequanox in laboratory, mesocosm, and field enclosure studies. One study indicated sensitivity of salmonid species and lake sturgeon (Acipenser fulvescens Rafinesque 1817) following exposure to Zequanox, however, the exposures were not conducted in a manner consistent with the product label. This laboratory study evaluated sublethal and lethal impacts of Zequanox on lake sturgeon and lake trout (Salvelinus namaycush Walbaum in Artedi, 1792) following exposures that were conducted consistent with a Zequanox open-water label application. Fish were exposed to 50 and 100 mg Zequanox active ingredient/L for 8 h and then held for an additional 33-d for post-exposure observation. No acute mortality was observed in either species, however, significant latent mortality (46.2%) was observed in lake trout that were exposed to 100 mg of Zequanox active ingredient/L for 8 h. At the termination of the 33d holding period, biologically minimal, yet statistically significant, differences were observed in the terminal weight of surviving lake sturgeon (range 20.17 to 21.49 g) and biologically, as well as, statistically significant differences were observed in the terminal weight of surviving lake trout (range 6.19 to 9.55 g). Histological evaluation of lake trout gastrointestinal tracts suggest that a different mode of action is responsible for the Zequanox exposure-related impacts to lake trout than the mode of action that induces zebra and quagga mussel mortality. Further research is required to determine if Zequanox sensitivity is limited to lake trout or if all salmonid species are vulnerable to exposure and to determine if native fish will avoid Zequanox exposure.