Stress proteins such as heat shock proteins (HSPs) and metallothioneins (MTs) play a key role in cellular protection against environmental stress. Marine ectotherms such as eastern oysters Crassostrea virginica are commonly exposed to multiple stressors including temperature and pollution by metals such as cadmium (Cd) in estuaries and coastal zones; however, the combined effects of these stressors on their cellular protection mechanisms are poorly understood. We acclimated C. virginica from populations adapted to different thermal regimes (Washington, North Carolina and Texas) at a common temperature of 12 degrees C, and analyzed their expression of MTs and HSPs (cytosolic HSP69, HSC72-77, HSP90 and mitochondrial HSP60) in response to the combined acute temperature stress and long-term Cd exposure. Overall, HSP and MT induction patterns were similar in oysters from the three studied geographically distant populations. HSP69 and MTs were significantly up-regulated by Cd and temperature stress implying their important role in cellular stress protection. In contrast, HSC72-77, HSP60 and HSP90 were not consistently induced by either acute heat or Cd exposure. The induction temperature for MTs was higher than for HSP69 (>28 degrees C vs. 20 degrees C, respectively), and MTs were more strongly induced by Cd than by temperature stress (to up to 38-94-fold compared by 3.5-7.5-fold, respectively) consistent with their predominant role in metal detoxification. Notably, heat stress did not result in an additional increase in metallothionein expression in Cd-exposed oysters suggesting a capacity limitation during the combined exposure to Cd and temperature stress. Levels of HSP69 and in some cases, HSC72-77 and HSP90 were lower in Cd-exposed oysters as compared to their control counterparts during heat stress indicating that simultaneous exposure to these two stressors may have partially suppressed the cytoprotective upregulation of molecular chaperones. These limitations of stress protein response may contribute to the reduced thermotolerance of oysters from metal-polluted environments.