Water treatment plants are often not effective in removing pharmaceuticals, personal care products or natural hormones from their effluents. To test the effects of these effluents on fish, we exposed male fathead minnows (Pimephales promelas) for 48h to effluents at two sites, one up-stream and the other down-stream from a water treatment plant. Gene expression profiling showed that significant changes occurred in the gonad of fish exposed below, compared to above the treatment plant and to laboratory control fish. Among the biological processes affected were the innate immune response, response to stress, control of homeostasis, control of transcription, metabolism, and cell communication. This work suggests that fish are impacted by exposures to the sewage treatment effluents and effects can be detected rapidly by gene expression profiling.