Synthetic and natural organic compounds derived from agricultural operations, residential development, and treated and untreated sanitary and industrial wastewater discharges can contribute contaminants to surface and ground waters. To determine the occurrence of these compounds in the lower Tallapoosa River watershed, Alabama, new laboratory methods were used that can detect human and veterinary antibiotics; pharmaceuticals; and compounds found in personal-care products, food additives, detergents and their metabolites, plasticizers, and other industrial and household products in the environment. Well-established methods for detecting 47 pesticides and 19 pesticide degradates also were used. In all, 186 different compounds were analyzed by using four analytical methods. The lower Tallapoosa River serves as the water-supply source for more than 100,000 customers of the Montgomery Water Works and Sanitary Sewer Board. Source-water protection is a high priority for the Board, which is responsible for providing safe drinking water. The U.S. Geological Survey, in cooperation with the Montgomery Water Works and Sanitary Sewer Board, conducted this study to provide baseline data that could be used to assess the effects of agriculture and residential development on the occurrence of selected organic compounds in the lower Tallapoosa River watershed. Twenty samples were collected at 10 sites on the Tallapoosa River and its tributaries. Ten samples were collected in April 2005 during high base streamflow, and 10 samples were collected in October 2005 when base streamflow was low. Thirty-two of 186 compounds were detected in the lower Tallapoosa River watershed. Thirteen compounds, including atrazine, 2-chloro-4-isopropylamino-6-amino-s-triazine (CIAT), hexazinone, metalaxyl, metolachlor, prometryn, prometon, simazine, azithromycin, oxytetracycline, sulfamethoxazole, trimethoprim, and tylosin, had measurable concentrations above their laboratory reporting levels. Concentrations were estimated for an additional 19 compounds that were detected below their laboratory reporting levels. The two most frequently detected compounds were the pesticides atrazine (19 of 20 samples) and simazine (13 of 20 samples). Tylosin, a veterinary antibiotic, was detected in 8 of 20 samples. Other compounds frequently detected at very low concentrations included CIAT and hexazinone (a degradate of atrazine and a pesticide, respectively); camphor (derived from personal-care products or flavorants), para-cresol (various uses including solvent, wood preservative, and in household cleaning products), and N,N-diethyl-m-toluamide (DEET, an insect repellent).