Abstract For many chemical compounds there is much information about their toxicity and biodegradability, but hardly any ecotoxicological investigations take into consideration how xenobiotic substances are integrated into complex biological systems. Here it is shown that 4-chloro-3-cresol (CMC), a chlorinated phenolic derivative used as a disinfectant and preservative, is completely eliminated within the process of natural self-purification, imitated in a lab-scaled river model. Biodegration of CMC occurred after the elimination of other organic compounds (synthetic sewage) which were easier to degrade. The nitrification of ammonia only started after CMC had been completely degraded. The kinetics of substrate oxidation (acetate) measured by oxygen consumption (Warburg-method) were inhibited noncompetitively by CMC. The gradual increase of the CMC concentration in the influent of the plant led to an increasing insensitiveness of the bacterial biocoenosis so that the kinetics of substrate oxidation in the presence of CMC resulted in a decrease of the inhibitory effect (increasing inhibition constant K i). The rate of CMC degradation referring to the biomass concentration increased with increasing CMC concentration in the influent, which indicated a growth of CMC-degrading bacteria within the total population. CMC degradation itself was inhibited at high concentrations (“substrate surplus inhibition”). In addition higher CMC concentrations in the influent of the river model led to a change of (1) the bacterial community and (2) the diversity of ciliates populations. In practice the separation of the processes of the elimination of easy biodegradable substances and of the degradation of CMC (e.g. activated sludge reactor and trickling filter) should be considered.