We conducted pilot-scale field experiments using nanofiltration membranes to lower the salinity and remove Se, As and other toxic contaminants from saline agricultural wastewater in the Imperial Valley, California, USA. Farmlands in the desert climate (rainfall - 7.4 cm/a) of Imperial Valley cover -200,000 ha that are irrigated with water (-1.7 km³ annually) imported from the Colorado River. The salinity (-850 mg/L) and concentration of Se (-2.5 μg/L) in the Colorado River water are high and evapotranpiration further concentrates salts in irrigation drainage water, reaching salinities of 3,000-15,000 mg/L TDS and a median Se value of -30 μg/L. Experiments were conducted with two commercially available nanofiltration membranes, using drainage water of varying composition, and with or without the addition of organic precipitation inhibitors. Results show that these membranes selectively remove more than 95% of Se, SO₄, Mo, U and DOC, and -30% of As from this wastewater. Low percentages of Cl, NO₃ and HCO₃, with enough cations to maintain electrical neutrality also were removed. The product water treated by these membranes comprised more than 90% of the wastewater tested. Results indicate that the treated product water from the Alamo River likely will have less than 0.2 μg/L Se, salinity of 300-500 mg/L TDS and other chemical concentrations that meet the water quality criteria for irrigation and potable use. Because acceptability is a major issue for providing treated wastewater to urban centers, it may be prudent to use the reclaimed water for irrigation and creation of lower salinity wetlands near the Salton Sea; an equivalent volume of Colorado River water can then be diverted for the use of increasing populations of San Diego and other urban centers in southern California. Nanofiltration membranes yield greater reclaimed-water output and require lower pressure and less pretreatment, and therefore are generally more cost effective than traditional reverse osmosis membranes.