Glutathione-related peptides (gamma-Glu-Cys)nGly, trivially known as phytochelatins (PCs), sequester Cd(II) and other heavy metals in all plants and some yeasts. However, the metal resistance levels may depend on factors such as the PC concentrations, their chain length and ability to incorporate labile sulfide. We show here that a highly Cd(II)-resistant mutant of yeast Candida glabrata exhibited Cd(II)-dependent formation of extremely high levels of PC-coated CdS quantum crystallites. The CdS crystallites were formed in the cytosol but finally accumulated in the vacuoles. Cd(II)-stimulated sulfide production required sulfate and was inhibited by both cysteine and methionine. GSH synthesis inhibition sensitized the resistant strain to Cd(II) indicating that GSH still provided primary defense against the metal ion.