We exposed fathead minnows (Pimephales promelas) to 7 concentrations of effluents from pulp mills at 4 Long-Term Receiving Water Study (LTRWS) sites. The primary objective of these investigations was to determine the potential for toxicity, particularly on fish reproduction, of the pulp mill effluents using laboratory tests. These tests were performed as LTRWS fish community assessments were being completed, thus results of the laboratory fish reproduction tests could be compared to in-stream fish community measurements. In general, bioindicators measured during the life-cycle tests, including gonadosomatic index (GSI), hepatosomatic index, condition factor, numbers of tubercles on heads of males and females, and gonadal histology did not show consistent patterns or dose response and did not predict effects on egg production. Gonadosomatic indexes and tubercles also did not indicate estrogenic or androgenic responses to the effluents during the life-cycle tests. The most consistently sensitive test endpoint showing a dose response was the 25% inhibition concentration (IC25) for egg production. Based on this endpoint all 4 effluents had effects on fish reproduction from 8% by volume to 100% effluent. However, in-stream effects on fish reproduction would not be expected based on these 4 life-cycle tests for any of the LTRWS stream sites. The mean effluent concentration in Codorus Creek, Pennsylvania, USA was approximately 32%, and the IC25 for the life-cycle test was 100% effluent, providing a margin of safety of approximately 3 times. The margins of safety at the other sites are much greater: 34 times for Leaf River, Mississippi, USA (IC25 = 69%, 2% mean receiving water concentration), 36 times for the McKenzie River, Oregon, USA (IC25 = 18%, 0.5% mean receiving water concentration), and 40 times for the Willamette River, Oregon, USA (IC25 = 8%, 0.2% mean receiving water concentration). Effects on fish numbers, diversity, and community structure due to the effluent were also not found during the LTRWS, which is consistent with these laboratory results. These findings indicate that in this case, when laboratory results combined with in-stream effluent concentrations suggest in-stream effects on fish population are not expected, the laboratory results are consistent with the in-stream observations. However, inferences about situations where laboratory results predict in-stream effects cannot be made from these data.