The chemicals 3-trifluoromethyl-4-nitrophenol (TFM) or a combination of TFM and 2a??,5-dichloro-4a??-nitrosalicylanilide (Bayer 73) have been used to control the sea lamprey (Petromyzon marinus) in the Great Lakes for about 20 yr. These chemicals cause some mortalities of Oligochaeta and Hirudinea, immature forms of Ephemeroptera (Hexagenia sp.), and certain Trichoptera, Simuliidae, and Amphibia (Necturus sp.). The combination of TFM and Bayer 73 may affect some Pelecypoda and Gastropoda, but its overall effects on invertebrates are probably less than those of TFM alone. Granular Bayer 73 is likely to induce mortalities among oligochaetes, microcrustaceans, chironomids, and pelecypods. No evidence exists that the lampricides have caused the catastrophic decline or disappearance of any species. The overall impact of chemical control of sea lampreys on aquatic communities has been minor compared with the benefits derived.