The Reedy River in South Carolina is affected by the urban area of Greenville, the third most populous city in the state, and by the effluents from two large-scale municipal wastewater treatment plants (WWTPs) located on the river. Riverine water chemistry was characterized using grab samples collected annually under spring season baseflow conditions. During the 4-year time period associated with this study, climatic variations included two severe drought spring seasons (2001 and 2002), one above-normal precipitation spring season (2003), and one below-normal precipitation spring season (2004). The influence of drought and human activities on the baseflow chemistry of the river was evaluated by comparing concentrations of dissolved anions, total metals, and other important water chemistry parameters for these different years. Concentrations of copper and zinc, common non-point source contaminants related to urban activities, were not substantially elevated in the river within the urban area under baseflow conditions when compared with headwater and tributary samples. In contrast, nitrate concentrations increased from 1.2-1.6 mg/l up to 2.6-2.9 mg/l through the urban stream reach. Concentrations of other major anions (e.g., sulfate, nitrate) also increased along the reach, suggesting that the river receives continuous inputs of these species from within the urban area. The highest concentrations of major cations and anions typically were observed immediately downstream from the two WWTP effluent discharge locations. Attenuation of nitrate downstream from the WWTPs did not always track chloride changes, suggesting that nitrate concentrations were being controlled by biochemical processes in addition to physical processes. The relative trends in decreasing nitrate concentrations with downstream distance appeared to depend on drought versus non-drought conditions, with biological processes presumably serving as a more important control during non-drought spring seasons.