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The objective of the present study was to investigate the responses of the chironomid communities (Diptera: Chironomidae) to environmental variables in four moderately and highly disturbed rivers located in one of the most degraded watersheds in South America. Sampling campaigns were carried out during 2014–2016 in four sites of the Matanza-Riachuelo basin. The physical-chemical and hydrological variables were measured and, the ecological indices were calculated and evaluated by ANOVA. The responses of Chironomidae to the environmental variables were evaluated by redundancy analysis (RDA), and the sampling sites were grouped according to the populations of chironomids and the main environmental variables. Finally, the Spearman correlation was made to determine which of these variables were significant. In total, 13 chironomid taxa were found in 36 samples during the study period. The greatest density registered belongs to Rheotanytarsus and Cricotopus. The ANOVA detected the greatest Chironomidae density and taxonomic richness in the sites with agricultural-urban impact. The changes in the distribution of Rheotanytarsus, Thienemanniella, and Polypedilum were mainly explained by the increase in current velocity, organic matter, and hardness, and the decrease of NH3 and BOD. On the other hand, Goeldichironomus, Chironomus, Parachironomus, Dicrotendipes, and Cricotopus were explained by the increase in conductivity, dissolved oxygen, and temperature, and the decrease of the variables NO3, BOD, and Cu. In addition to this, the sites with urban-agricultural impact were clearly separated from sites with urban-industrial impact. The last one was more related to the increase in BOD, Cu, and NO3 that indicates moderate to poor water quality. In conclusion, we can infer that the physical and chemical variables are correlated with changes in the structure and distribution of the chironomid community and there are genera that respond differently at high and intermediate situations of disturbances. This knowledge contributes to the execution of strategies for the conservation and restoration of the lotic ecosystems. [ABSTRACT FROM AUTHOR]