Samples were collected from 16 base-flow events and a minimum of 10 stormflow events between July 1998 and October 2000 to characterize the effects of wastewater and combined sewer overflows on water quality in the Blue River Basin, Kansas City, Missouri and Kansas. Waterquality effects were determined by analysis of nutrients, chloride, chemical and biochemical oxygen demand, and suspended sediment samples from three streams (Blue River, Brush Creek, and Indian Creek) in the basin as well as the determination of a suite of compounds known to be indicative of wastewater including antioxidants, caffeine, detergent metabolites, antimicrobials, and selected over-the-counter and prescription pharmaceuticals. Constituent loads were determined for both hydrologic regimes and a measure of the relative water-quality impact of selected stream reaches on the Blue River and Brush Creek was developed. Genetic fingerprint patterns of Escherichia coli bacteria from selected stream samples were compared to a data base of knownsource patterns to determine possible sources of bacteria. Water quality in the basin was affected by wastewater during both base flows and stormflows; however, there were two distinct sources that contributed to these effects. In the Blue River and Indian Creek, the nearly continuous discharge of treated wastewater effluent was the primary source of nutrients, wastewater indicator compounds, and pharmaceutical compounds detected in stream samples. Wastewater inputs into Brush Creek were largely the result of intermittent stormflow events that triggered the overflow of combined storm and sanitary sewers, and the subsequent discharge of untreated wastewater into the creek. A portion of the sediment, organic matter, and associated constituents from these events were trapped by a series of impoundments constructed along Brush Creek where they likely continued to affect water quality during base flow. Concentrations and loads of most wastewater constituents in the Blue River and Indian Creek were significantly greater than in Brush Creek, especially during base flow. However, wastewater indicator compound concentrations were sometimes greater in some Brush Creek stormflow samples. Selected stream reaches along the mid-portion of Brush Creek showed higher effects relative to other sites, primarily because these sites were in impounded reaches with the greatest density of wastewater inputs, or had relatively small drainage areas.