As part of the sea lamprey control program in the Great Lakes, a suite of about 150 sea lamprey producing streams have been regularly treated with the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) every 3 to 5 years since 1958. State, provincial, and tribal agencies in the basin supported the use of TFM and urged that the risk to nontarget organisms be minimized. To determine the response of riffle macroinvertebrate communities to repeated TFM treatments over several years, paired samples were taken at control and treatment sites during 1986 to 1995 on four Great Lakes tributaries: the Bois Brule, West Branch Whitefish, Boardman, and Sturgeon (tributary to Cheboygan River system) rivers. Macroinvertebrates were collected in spring and fall by a standard traveling kick method. The communities were described with several metrics, and general linear models were used to test for different patterns of response in the paired control and treatment sites. Relative abundance of the class Oligochaeta, relative abundance of the genus Ephemerella, the Bray-Curtis similarity index (at the taxonomic level of order), EPT genus richness (the number of genera in the orders Ephemeroptera, Plecoptera, and Trichoptera), and total genus richness all increased more at the treatment sites than at the control sites after TFM application. The greater increase in abundance, similarity, and richness at the treatment sites was an indication of recovery in the treatment sites, where a short-term response to TFM was followed by a several-year rebound. TFM treatments in this study during the 1980s and 1990s had no long-lasting effects on riffle macroinvertebrate communities.