The objective of this study was to examine (i) the biochemical responses of rainbow trout exposed to sublethal water concentrations of the metals cadmium (Cd) (1.5 microg l(-1)) and zinc (Zn) (150 microg l(-1)); and (ii) the potential combined effects when applied in mixture (Cd/Zn) with and without co-exposure to model organic chemicals 3,3',4,4'-tetrachlorobiphenyl (PCB77) (1 mg kg (-1)) and 17beta-oestradiol (E2) (0.5 mg kg(-1)). After 21 days of exposure, several biomarkers were assessed in the liver (enzymatic and nonenzymatic antioxidants, heat shock proteins [HSP70 and HSP60], ethoxyresorufin-O-deethylase [EROD]) and in the plasma (vitellogenin [Vtg], aminotransferases). Plasma aminotransferases were not affected, whereas the other biomarkers showed different patterns of response depending on the treatment. For example, Cd, and Zn to a lesser extent, induced an adaptive response in the liver shown by an increase in antioxidant defences (total glutathione [GSH], superoxide dismutase, Trolox equivalent antioxidant capacity [TEAC]), without any impairment of GSH redox status or induction of heat shock proteins. Antagonistic effects were observed in GSH-related biomarkers after Cd/Zn exposure. PCB77 strongly induced EROD activity, HSP70 and TEAC. Co-exposure with metals did not modulate significantly the effects of PCB77. E2 induced Vtg and inhibited liver antioxidants and basal EROD activity. These inhibitory effects were suppressed in fishes exposed to E2 + Cd/Zn, suggesting additive effects of E2 and metals. In addition, E2-induced Vtg was not altered by metals. Multivariate analyses confirmed some correlation between the biomarkers. The use of complementary biomarkers is necessary to discriminate different treatments and to highlight interactive effects.