The response of the pathogenic yeast Candida albicans to the silver(I) perchlorate salt (AgClO(4)) was assessed. By employing an anti-phospho-p38 MAPK antibody, dual phosphorylation of a high osmolarity protein (Hog1p) in C. albicans in the presence of AgClO(4) was demonstrated. Phosphorylation of C. albicans Hog1p in response to hydrogen peroxide or AgClO(4) resulted in the translocation of this mitogen-activated protein (MAP) kinase to the nucleus. Nuclear translocation of C. albicans activating protein-1 (Cap1p) was demonstrated by Western blot analysis and detected using polyclonal anti-Cap1p antibody. Upon AgClO(4)-induced translocation of Cap1p there was a concomitant activation of genes coding for glutathione reductase-1 and Mn-superoxide dismutase but no increase in the expression of flavin oxidoreductase or mitochondrial processing protease was recorded. In addition, exposure to AgClO(4) increased the activity of superoxide dismutase, glutathione reductase and catalase. The activation of C. albicans oxidative stress response genes and enzymes following exposure to AgClO(4) is evidence of the generation of oxidative stress within this medically important yeast.