Toxicants have both sub-lethal and lethal effects on aquatic biota, influencing organism fitness and community composition. However, toxicant effects within ecosystems may be altered by interactions with abiotic and biotic ecosystem components, including biological interactions. Collectively, this generates the potential for toxicant sensitivity to be highly context dependent, with significantly different outcomes in ecosystems than laboratory toxicity tests predict. We experimentally manipulated stream macroinvertebrate communities in 32 mesocosms to examine how communities from a low-salinity site were influenced by interactions with those from a high-salinity site along a gradient of salinity. Relative to those from the low-salinity site, organisms from the high-salinity site were expected to have greater tolerance and fitness at higher salinities. This created the potential for both salinity and tolerant-sensitive organism interactions to influence communities. We found that community composition was influenced by both direct toxicity and tolerant-sensitive organism interactions. Taxon and context-dependent responses included: (i) direct toxicity effects, irrespective of biotic interactions; (ii) effects that were owing to the addition of tolerant taxa, irrespective of salinity; (iii) toxicity dependent on sensitive-tolerant taxa interactions; and (iv) toxic effects that were increased by interactions. Our results reinforce that ecological processes require consideration when examining toxicant effects within ecosystems.