We evaluated the sensitivity of larval sea lampreys Petromyzon marinus to the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) in a series of toxicity tests in spring and summer. Although noted previously, the seasonal variation in sensitivity to TFM had never been tested as a means of reducing TFM usage in stream treatments. A preliminary study consisted of three spring and four summer static toxicity tests conducted at 12??C. A more comprehensive study consisted of 12 spring and summer paired flow-through toxicity tests conducted both at seasonal water temperatures and at 12??C. The sensitivity of larval sea lampreys to TFM was greater in spring than in summer. The preliminary static toxicity tests indicated that the concentration of TFM needed to kill larval sea lampreys in spring (May and June) was about one-half that required in summer (August); the concentrations lethal to 50% and 99.9% of the test animals (the LC50 and LC99.9 values) were less in spring than in summer. Analysis of variance of the flow-through toxicity data indicated that season significantly affected both the LC50 and LC99.9 values. For all 12 paired flow-through toxicity tests, the spring LC50 and LC99.9 values were less than the corresponding summer values. For 9 of the 12 paired flow-through toxicity tests, the dose-response toxicity lines were parallel and allowed statistical comparison of the LC50 values. The spring LC50 values were significantly lower than the summer values in eight of the nine tests. Verification of a seasonal variation in the sensitivity of larval sea lampreys to TFM will allow inclusion of this factor in the selection model currently used by both the U.S. Fish and Wildlife Service and the Department of Fisheries and Oceans-Canada to schedule lampricide stream treatments. ?? Copyright by the American Fisheries Society 2008.