The effect of wastewater irrigation on resistance of poplar trees to the cottonwood leaf beetle, Chrysomela scripta F., was investigated. Five Populus clones were tested in a greenhouse for their effects on the survival, fresh pupal weight, and development time (from egg to adult) of the cottonwood leaf beetle when they were irrigated with either wastewater or freshwater. Foliar concentrations of nitrogen, mineral elements (P, Mn, Mg, Ca, Na, K), phenolic glycosides, and leaf toughness also were measured to understand the potential mechanisms of resistance to the cottonwood leaf beetle. C. scripta performance was negatively affected by irrigation with wastewater; both survival and pupal weight were reduced. Performance also varied among clones and was the worst on Populus fremontii Watson variety wislenzensii, a native species. Leaf toughness and foliar N level were not affected by the irrigation treatment and were not correlated with larval growth and survival. Among minerals, foliar concentrations of sodium increased with wastewater irrigation, and were related negatively to pupal weights. Foliar magnesium also was influenced by the irrigation treatment but it was not correlated with C. scripta performance. Manganese varied with clone, but not with the type of water used for irrigation, and was correlated negatively with survival and related positively to development time. Differences in phenolic glycosides were observed between treatments and among clones, but there were no detectable relationships between phenolic glycosides and C. scripta performance.