The U.S. Geological Survey and the National Park Service cooperated on a study to determine the occurrence of wastewater indicator compounds including nutrients; organic wastewater compounds (OWCs), such as compounds used in plastic components, surfactant metabolites, antimicrobials, fragrances, and fire retardants; and pharmaceuticals in the St. Croix National Scenic Riverway in Minnesota and Wisconsin. Samples of treated wastewater effluent from two wastewater-treatment plants (WWTPs), located in St. Croix Falls, Wisc. (SCF-WWTP) and Taylors Falls, Minn. (TF-WWTP), were collected from 2007 to 2008. During this time, surface-water and bed-sediment samples from the St. Croix River below Sunrise River near Sunrise, Minn., upstream from the two WWTPs (Sunrise site), and from the St. Croix River above Rock Island near Franconia, Minn., downstream from the WWTPs (Franconia site), also were collected. The Franconia site was selected because of the two large WWTP discharge points and the presence of mussel beds in this area of the St. Croix River. A variety of OWCs and pharmaceuticals were detected in wastewater effluent from both WWTPs. Compounds detected varied between the two WWTPs and varied over time from samples collected at each site. The concentration and numbers of OWCs detected were greater in the wastewater effluent samples from SCF-WWTP (38 OWCs and 7 pharmaceuticals detected) than from TF-WWTP (20 OWCs and 3 pharmaceuticals detected). Four endocrine active compounds, compounds known to affect the endocrine systems of fish-4-nonylphenol, 4-nonylphenol diethoxylate, acetyl hexamethyl tetrahydronaphthalene, and hexahydrohexamethyl cyclopentabenzopyran-also were detected in effluent samples from both WWTPs. Concentrations of phosphate flame retardants were greater in effluent from SCF-WWTP than from TF-WWTP with the concentration of tris(2-butoxyethyl) phosphate greater than 200 micrograms per liter. Seven OWCs, including one endocrine active compound, and two pharmaceuticals were detected in surface-water samples from the Sunrise site. Twelve OWCs and three pharmaceuticals were detected in surface-water samples from the Franconia site. Eighteen OWCs were detected in bed-sediment samples from the Sunrise site, whereas 21 OWCs were detected in bed-sediment samples from the Franconia site. Eight pharmaceuticals were detected in bed-sediment samples from both sites. The results of this study indicate that aquatic biota in the St. Croix River are exposed to a wide variety of organic contaminants that originate from diverse sources including WWTP effluent. The data on wastewater indicator compounds indicate that exposures are temporally and spatially variable and that OWCs may accumulate in bed sediment. These results also indicate that OWCs in water and bed sediment increase downstream from discharges of wastewater effluent to the St. Croix River; however, the presence of OWCs in surface water and bed sediment at the Sunrise site indicates that potential sources of compounds, such as WWTPs or other sources, are upstream from the Taylors Falls-St. Croix Falls area.