Cadmium is a long-living heavy metal, abundantly present in the environment, which accumulates in the body. In this study, we investigated the effects of cadmium on the expression of molecular chaperones, and of certain cell-specific proteins, in a variety of brain cell types in culture, namely primary cultures of rat cortical neurons and astrocytes, a brain capillary endothelial cell line (RB4E.B cells), and pheochromocytoma cells (PC12), induced or not to differentiate by NGF treatment. The metal induces a dose-dependent increase of Hsp70 in all cell types. Responses to the metal are cell-specific in the case of Hsc70 and Hsp90: i) in astrocytes, as well as in PC12 cells, cadmium has no significant effect; ii) in endothelial cells, an increase of both proteins is clearly observable from 20 microM cadmium; iii) both Hsp90 and Hsc70 decrease in neurons treated with high doses of cadmium. Damage to the cytoskeleton in treated cells was also evident. Finally, we report that the metal at high doses induces a decrease of PIPPin (also known as CSD-C2), a putative RNA-binding protein highly expressed in neurons and probably involved in the regulation of histone replacement variant expression.