Integrated management of sea lampreys (Petromyzon marinus) in the Great Lakes relies primarily on the application of the lampricide, 3-trifluoromethyl-4-nitrophenol (TFM), into streams to eradicate larval populations. From 1979 to 1999, 1,282 lampricide treatments were conducted on 316 streams. During the period from 1979 to 1989, an average of 52,904 kg active ingredient (kg/yr) of TFM was applied annually. This was reduced to an average of 38,698 kg/yr for the decade of 1990 to 1999. This reduction was enhanced in the years of 1995 to 1999 to an average of 34,120 kg/yr, a 36% reduction from that used in 1979 to 1989. Efforts to minimize non-target mortality and to reduce applications of pesticides into the environment were the impetus for this reduction. The three factors that influenced annual TFM use were number of streams treated and conditions during treatment, the adaptation of several management techniques to reduce TFM use, and alternative control techniques. Changes in streams selected for treatment and scheduling treatments during low stream discharge accounted for about 26% of the reduction in annual TFM use. The management techniques include lampricide treatments with a TFM/niclosamide mixture, pH/alkalinity prediction models to determine minimum TFM requirements, maintaining lampricide concentrations at or near minimum levels, computer modeled treatment planning, and single block treatments, and were responsible for about 70% of the reduction observed in the 1990s. Alternative control techniques (barrier dams) accounted for only 4% of the reduction.