Modernizing water quality criteria to predict how contaminants affect natural aquatic communities requires that we utilize data obtained across multiple lines of evidence, including laboratory, mesocosm, and field studies. We report the results of 29 mesocosm experiments conducted from 1994 to 2017 at the Colorado State University Stream Research Laboratory (Fort Collins, CO, USA). The primary goal of the present study was to quantify responses of aquatic insect communities collected from 8 different locations to different combinations of cadmium (Cd), copper (Cu), iron (Fe), and zinc (Zn). Treatments that included Cu or Fe, either alone or in combination with other metals, were especially toxic to aquatic insects. The results showed that effects of metals were context dependent and varied significantly among the 8 sites where communities were collected. In particular, effects on communities from smaller streams were significantly greater than those from larger streams. Our analyses also showed that several morphological (body size, shape, gills, degree of sclerotization) and life history (voltinism) traits were significantly correlated with sensitivity to metals. Across all taxa and experiments, aquatic insects broadly classified as small (maximum body length <8 mm) were significantly more sensitive to metals than medium or large individuals. These findings demonstrate the advantages of integrating results of mesocosm experiments with species traits to develop a mechanistic understanding of biotic and abiotic factors that influence community responses to contaminants. Environ Toxicol Chem 2019;38:2486-2496. © 2019 SETAC.