It is generally accepted that lipid peroxides play an important role in the pathogenesis of free radical-induced cellular injury and that endogenous thiols are vital in cellular defense against oxidative stress. The purpose of this study was to investigate in cultured human skin fibroblasts the effect of oxidative stress on the synthesis of heat shock protein (HSP70) and on the sulfhydryl group content in the absence and presence of alpha-tocopherol as an antioxidant compound. The interesting observation emerging from this study was a marked increase in malonaldehyde and fluorescent peroxide levels associated with a significant thiol depletion and induction of HSP70 stress proteins observed in primary cultures of normal human skin fibroblasts subjected to heat shock or incubated with hydrogen peroxide. These changes were significantly reduced in the presence of alpha-tocopherol. Our findings suggest a correlation between the mechanisms of oxidative stress, antioxidants and HSP70 induction, which can be assessed to evaluate either the perturbation of skin oxidant/antioxidant balance or the protection afforded by antioxidant test compounds.