This study compared the effects of increased endogenous cortisol levels and/or sublethal Cu exposure on Cu accumulation and stress protein levels (HSP70) in the freshwater common carp, Cyprinus carpio. Fish were exposed to either increased levels of endogenous cortisol (200 ng/ml) or sublethal Cu concentrations (1.9 microM, approximately 20% of the acute 96-h median lethal concentration [LC50]) alone or were pretreated by elevating plasma cortisol levels prior to Cu exposure to evaluate whether interactions between both treatments occurred. Cortisol resulted in decreased Cu levels and a decreased Cu accumulation on a short-term basis (4 h). After 96 h of Cu exposure, cortisol pretreatment resulted in augmented Cu accumulation. Exposure to Cu increased HSP70 levels in gills, erythrocytes, and liver and decreased levels in brain and kidney. No clear relationship to Cu tissue levels was observed. Increased cortisol levels or treatment with cortisol before Cu exposure decreased the HSP70 response. We can conclude that cortisol elevation results in a lower HSP70 response and thus reduces the protection against cellular stress during metal accumulation. After an initial decrease in Cu accumulation, cortisol elevation eventually stimulates metal accumulation.