The zebra mussel Dreissena polymorpha, an exotic invasive species, poses a major threat to North American fish management programs and the aquaculture industry. Fish hatcheries may become infected with zebra mussels from a variety of sources, including the water supply, fish shipments, boats, and equipment. The hatcheries could then serve as agents for the overland dispersal of zebra mussels into stocked waters and to other fish hatcheries. We evaluated the effectiveness and safety of aquaculture chemicals for use in controlling zebra mussels in fish hatcheries and preventing dispersal of veligers during fish transport. Chemicals were evaluated for use in fish transport and as disinfectants for ponds and equipment. Standardized static toxicity tests were conducted with representative species of warmwater, coolwater, and coldwater fishes and with larval (3-d-old veligers), early juvenile (settling larvae), and adult zebra mussels. Chemical concentrations and exposure durations were based on recommended treatment levels for fish, eggs, and ponds. Recommended treatment levels were also exceeded, if necessary, to establish lethal levels for zebra mussels of different developmental stages. Our results indicate that some chemicals currently in use in hatcheries may be effective for controlling zebra mussels in various operations. Chloride salts were the safest and most effective therapeutants tested for use in fish transport. The toxicity of chloride salts to fish varied among species and with temperature; only one treatment regime (sodium chloride at 10,000 mg/L) was safe to all fish species that we tested, but it was only effective on veliger and settler stages of the zebra mussel. Effective disinfectants were benzalkonium chloride for use on equipment and rotenone for use in ponds after fish are harvested. The regulatory status of the identified chemicals is discussed as well as several nonchemical control alternatives.