Chemical irritants are able to produce several biological modifications of the skin, including the direct or indirect production of cytokines and reactive oxygen species leading to an inflammatory reaction. This report examines the existence of a possible correlation between the skin sensitivity to the irritant sodium dodecyl sulphate (SDS) and the activity of the enzymatic antioxidants. In twenty-three healthy subjects the evaluation of the epidermal and peripheral blood mononuclear cells (PBMCs) activities of Superoxide Dismutase (SOD) and Catalase (Cat) demonstrate a significant correlation (r= 0,85 and p< 0,005 for SOD, and r= 0,87 and p< 0,0001 for Cat). Based on this result, on a further group of normal subjects (n=13) we studied the link between the threshold dose of skin reactivity to SDS and the activities of the enzymatic antioxidants in PBMCs. The degree of skin modification induced by SDS, applied at different concentrations for 24 hrs, was determined by means of Trans Epidermal Water Loss (TEWL), Erythemal Index or by Visual Score (VS). The minimal dose of the irritant capable of inducing skin modifications, was significantly correlated with SOD (r=0,77) and Cat (r=0,81) activities in PBMCs, and the modification ofTEWL or EI were inversely correlated with levels of antioxidants in PBMCs (r=-0,62 for SOD and r=-0,66 for Cat). Our results indicate that the skin reactivity to irritants can be modulated by the levels of antioxidants, and suggest a possible therapeutical approach in preventing irritant contact dermatitis.The skin represents the borderline between the body and the environment and is continuously exposed to several physical and chemical oxidative stimuli. Against the oxidative stress the skin is armed with a complex system of antioxidants, including both low molecular weight substances and enzymatic networks. The antioxidant enzymes (glutathione reductase, peroxidase, superoxide dismutase, catalase, etc) interact with the low molecular weight substances (vitamin E, vitamin C, glutathione, ubiquinol, ascorbate) giving a sophisticated defence system able to ensure the physiological cellular activity (1). The ability to counteract dangerous stimuli derives from the optimal equilibrium between the different antioxidants. For example, ubiquinol-IO recycles a-tocopherol whereas glutathione reduces the oxidized form of ascorbate (2). Moreover, the antioxidant defence system is involved at different levels, including prevention, interception, and repair of oxidative stress-induced damage. Firstly, the skin buffers the oxidative insult by scavenging the reactive oxygen species (i.e. by means of Catalase and Superoxide dismutase). Subsequently, lipoperoxidative processes can be prevented by antioxidants, such as tocopherols and l3-carotene. Finally, the damaged proteins, lipids and DNA can be repaired by several enzymatic systems: the lipid hydroperoxides are released from phospholipids by phospholipases and the free hydroperoxides are reduced by glutathione peroxidase; thioredoxin/thioredoxin reduc...