Irrigation drain waters entering Stillwater Wildlife Management Area (SWMA) in south-western Nevada contain elevated levels of salinity and several inorganic contaminants (As, B, Cu, Li, Mo, and Sr). Mortalities of fish and waterfowl at the management area are believed to be associated with the poor water quality of the drains. The objective of the present study was to use fresh-water and saltwater animals to distinguish between the toxic effects of salinity and contaminants in effluent samples collected from irrigation drain waters. Static acute effluent tests were conducted with water collected from four sites at SWMA. Animals acclimated or cultured in fresh water (fathead minnows, Pimephales promelas; amphipods, Hyalella azteca; cladocerans, Daphnia magna) and salt water (striped bass, Morone saxatilis; amphipods, Hyalella azteca; and cladocerans, Daphnia magna) were used to separate toxic effects of salinity from the effects of inorganic contaminants in the drain water. One drain water (TJ drain, salinity 19 parts per thousand (grams per liter), osmolality 503 mmol/kg, hardness 3,780 mg/L as CaCO₃) was toxic only to freshwater animals and saltwater cultured daphnids; water from a receiving pond (Pintail Bay, salinity 23 g/L, osmolality 542 mmol/kg, hardness 830 mg/L as CaCO₃) was toxic to both freshwater and saltwater animals. Acute tests conducted with reconstituted waters representative of the Pintail Bay sample indicated that atypical ion ratios were toxic to striped bass and amphipods, even without the addition of inorganic contaminants. However, the addition of inorganic contaminants representative of the Pintail Bay sample increased the toxicity of this reconstituted water. These findings indicate that the toxicity of the TJ drain sample was related mainly to elevated salinity and that the toxicity of the Pintail Bay sample was a function of inorganic contamination and atypical ion ratios in combination with elevated salinity.