The biology of the zebra mussel is reviewed as it relates to water‐quality problems in rivers. A relationship between population densities of the zebra mussel and their respiration demands for oxygen is developed, which can be used to support the analysis of the impact of zebra mussel infestation on the oxygen resources of streams and rivers. Dramatic changes in the water quality of the Seneca River, N.Y., a major tributary to Lake Ontario, have been brought about by zebra mussel infestation. These changes are documented from 3 years of monitoring data. The infestation converted the Seneca River from a turbid, phytoplankton‐rich, nutrient‐depleted system, with nearly saturated oxygen concentrations, to a river with high clarity, low‐phytoplankton concentrations, enriched in dissolved nutrients, with greatly undersaturated oxygen concentrations. The degradation of oxygen resources was severe enough to cause violations of New York State standards for daily minimum and daily average concentrations for a number of days in the late summer of 1993. The associated loss in the waste assimilative capacity of the river is confounding waste discharge management and planning efforts in the river basin. This form of degradation is expected for other systems as the zebra mussel infestation spreads. The impact is expected to be greatest in rivers and streams with high concentrations of phytoplankton, large areas of rock substrate, and limited reaeration capacity.