Forty-seven chemicals having potential for preventing the attachment of zebra mussels Dreissena polymorpha were identified and tested. For each chemical, 15 zebra mussels (5–8-mm shell length) in each of two replicates and six treatments were exposed for 48 h followed by a 48-h postexposure period in untreated water. Eleven of the chemicals inhibited the reattachment of zebra mussels after the 48-h exposure; eight had EC50 values ranging from 0.4 to 5.4 mg/L, and three had EC50 values ranging from 19.4 to 29.0 mg/L. Based on an analysis of chemical cost, solubility in water, anticipated treatment concentrations, and potential hazards to humans or the environment, three of the most promising chemicals, all antioxidants, (butylated hydroxyanisole [BHA], tert-butylhydroquinone, and tannic acid) were tested on nontarget fish (bluegill, Lepomis macrochirus; channel catfish, Ictalurus punctatus; and rainbow trout, Oncorhynchus mykiss). These chemicals were not selectively toxic to zebra mussels; only the tests with bluegill and BHA and with channel catfish and tannic acid had 48-h LC50 values greater than the concentrations effective for preventing the reattachment of zebra mussels. Although the attachment of zebra mussels can be prevented with selected antioxidants, an alternative formulation should be investigated to minimize effects on nontarget organisms, such as fish.