The biological defence mechanism called MXR or MXD for multixenobiotic resistance or defence protects cells against the entry and the accumulation of xenobiotics. As the defence is modulated by man made chemicals, MXR is used as a biomarker of organisms’ exposure to environmental contamination. However, to reliably assess and evidence MXR induction, the use of a reference level is required. In this context, we focused on MXR background level in a freshwater bivalve, the zebra mussel Dreissena polymorpha, in order to propose its use as a reference during MXR evaluation. We monitored the MXR transport activity in mussels collected either in a natural population or in a caged population and then transplanted to clean water in the laboratory. The results showed that MXR activity was decreased to its baseline level after an eight to nine day depuration period (13. 1±3. 1; 7±2. 6; 13. 7±3. 9pmolRBmin−1 org−1 after three experiments of laboratory depurations). Moreover, significant MXR induction was measured in depurated zebra mussels exposed to contaminated sites (39. 6±3. 7; 59. 2±20. 3pmolRBmin−1 org−1 after two experiments of field exposure), showing that the laboratory depuration did not affect the induction potential. The MXR responses (decrease as well as increase) occurred in few days and were highly significant, highlighting its reactivity in zebra mussels. Finally, this paper confirms the usefulness of MXR as a tool in biomonitoring studies and provides a protocol for field experiments that enables to establish and use the background level of MXR activity as a reference. [Copyright &y& Elsevier]