The objective was to describe and model varia- tion patterns in individual fish responses to contaminants among estuaries, season and gender. Two hundred twenty- seven adult European flounders were collected in two sea- sons (winter and summer) in four estuaries along the Bay of Biscay (South West France), focusing on a pristine system (the Ster), vs. three estuaries displaying contrasted levels of contaminants (the Vilaine, Loire and Gironde). Twenty-three variables were measured by fish, considering the load of contaminants (liver metals, liver and muscle persistent organic pollutants, muscle polycyclic aromatic hydrocar- bons); the gene expression (Cyt C oxydase, ATPase, BHMT, Cyt P450 1A1, ferritin); the blood genotoxicity (Comet test); and liver histology (foci of cellular alteration–tumour, steatosis, inflammation, abnormal glycogen storage). Ca- nonical redundancy analysis (RDA) was used to model these variables using gender, season and estuary of origin as explanatory variables. The results underlined the homo- geneity of fish responses within the pristine site (Ster) and more important seasonal variability within the three contam- inated systems. The complete model RDA was significant and explained 35 % of total variance. Estuary and season respectively explained 30 and 5 % of the total independent variation components, whilst gender was not a significant factor. The first axis of the RDA explains nearly 27 % of the total variance and mostly represents a gradient of contami- nation. The links between the load of contaminants, the expression of several genes and the biomarkers were ana- lysed considering different levels of chemical stress and a possible multi-stress, particularly in the Vilaine estuary.