The toxicity of water from three rivers in the Santee-Cooper drainage of South Carolina was evaluated in a series of on-site studies with larval striped bass Morone saxatilis. Mortality and swimming behavior were assessed daily for larvae exposed to serial dilutions of water collected from the Santee, Congaree, and Wateree rivers. After 96 h, cumulative mortality was 90% in the Wateree River, and a dose–response pattern was evident in serial dilutions of the water. Larvae exposed to water from the Santee and Congaree rivers swam lethargically, but no appreciable mortality was observed. Acutely toxic concentrations of inorganic contaminants were not detected in the rivers; however, pentachloroanisole, a methylated by-product of pentachlorophenol, was twice as high in the Wateree River as it was in the other two rivers. Phenolic compounds may have contributed to larval mortality in the Wateree River and to lethargic activity of larvae in the Santee and Congaree rivers.