Vitamin E is the most important lipophilic antioxidant. Oxidative injuries are prevented or minimized by vitamin E supplementation. Various physiological and pathological situations are accompanied by vitamin E deficiency. However, it is not clear whether alimentary vitamin E deficiency in itself constitutes oxidant stress that induces appropriate responses, which, in turn, can be avoided by adequate vitamin E supplies, or whether the remaining cellular antioxidants compensate a temporary vitamin E deficiency. We studied effects of the dietary vitamin E status on cellular vitamin E levels and on the expression of heat shock proteins (HSPs) in alveolar type II cells and liver. The expression of HSPs, representing an early and very sensitive marker of cellular stress, was compared with the activity of antioxidative enzymes. Vitamin E depletion caused a substantial increase in HSP32 in alveolar type II cells, whereas in liver there was a marked increase in HSP70. The activity of the antioxidant enzymes, however, did not change significantly. A reversal of HSP expression to almost normal levels was seen after vitamin E resupplementation. These results indicate that, under normal conditions, a suboptimal supply of vitamin E to rats exposes the alveolar type II cells and the liver to reversible cellular stress.