1. Degradation of freshwater ecosystems is a major concern worldwide. Agriculture introduces multiple stressors to streams, presenting a challenge for freshwater managers who must understand the relative strengths of individual stressor effects and their combined multiple-stressor effects.
2. Using a replicated regression design, we manipulated levels of fine sediment and nutrients to create a broad eight-point gradient for each stressor across 128 stream mesocosms to determine the shapes of macroinvertebrate responses after 21 days of exposure.
3. Subsidy–stress response patterns occurred along both stressor gradients. Sediment addition provided an initial subsidy for some pollution-tolerant taxa and total macroinvertebrate density, but produced consistently negative effects for other taxa, total taxon richness and the density and richness of pollution-sensitive Ephemeroptera, Plecoptera, Trichoptera (EPT) taxa. Nutrient enrichment provided an initial subsidy for densities of two common EPT taxa, total EPT density, macroinvertebrate and EPT taxon richness.
4. Few macroinvertebrate variables were affected by a single stressor (always fine sediment). The majority of responses were additive multiple-stressor patterns, although Chironomidae density and EPT taxon richness followed complex synergistic patterns.
5. Fine sediment was a much more pervasive stressor than augmented nutrient concentrations. Overall, macroinvertebrate traits responded to stressors as strongly as community variables or individual taxa.
6. Synthesis and applications. Managing both fine sediment and nutrient inputs from agriculture is crucial to achieve good stream condition but priority should be given to minimizing fine sediment, which should be maintained below a threshold of 5% cover and 0·5-mm depth. Managers also need to be wary of interactive multiple-stressor effects because ecological outcomes of an increase in stressor load may be worse than predicted based on the knowledge of single-stressor effects.