The effects of various water chemistry parameters on the toxicity of copper to larval fathead minnows were investigated. Increased pH, hardness, sodium, dissolved organic matter, and suspended solids each caused toxicity to decrease on the basis of total copper concentrations. In contrast, added potassium resulted in increased toxicity. Alkalinity had no observed effect on total copper LC50s, but its effects might have been masked by those of the cations added with it. In most cases, the effects of water chemistry were found to be similar for different endpoints (growth, survival at different durations), but there were differences in the relative magnitude of some effects across these endpoints. Over all experimental treatments, 96-h total copper LC50s varied 60-fold. Every water chemistry parameter also caused toxicity to vary significantly when expressed on the basis of cupric ion selective electrode measurements, sometimes more so than on the basis of total copper. Therefore, this study does not support attributing to cupric ion a singular importance in regulating toxicity to this test organism. A variety of copper species might be contributing to toxicity and it is evident that toxicity is also affected by water chemistry in ways not related to copper speciation.