Solar radiation induces suppression of the local effector mechanisms involved in immune responses to recall antigens. By using a low-dose solar-simulated radiation protocol, we investigated whether oral supplementation of the antioxidants RRR-alpha-tocopherol combined with L-ascorbic acid prevented radiation-induced suppression of the contact hypersensitivity response to nickel sulfate. In a prospective, randomized study, nickel-sensitive individuals were given RRR-alpha-tocopherol 2 g/d oral supplements combined with L-ascorbic acid 3 g/d for 50 d (group 1). Individuals in the control group were given a placebo (group 2). The reaction to a standardized patch test with serial dilutions of nickel sulfate and the irritant skin reaction to sodium lauryl sulfate were assessed by visual grading and by reflectance spectrophotometry in radiation-exposed and nonexposed skin 50 days after supplementation. Results showed that the contact hypersensitivity response to the recall antigen nickel sulfate was significantly suppressed in the radiation-exposed skin of those who took the placebo. Supplementation with RRR-alpha-tocopherol combined with L-ascorbic acid significantly protected against the radiation-induced suppression of the contact hypersensitivity response to nickel sulfate. The irritant reaction to sodium lauryl sulfate was not suppressed by radiation, and antioxidant supplementation did not modulate this response. In conclusion, a combination therapy of systemic high-dose RRR-alpha-tocopherol combined with L-ascorbic acid prevented solar-simulated radiation-induced suppression of the local immune response to the recall antigen nickel sulfate in human skin. This immunoprotective effect of combined RRR-alpha-tocopherol and L-ascorbic acid could be exploited for the prevention of solar radiation-induced skin cancer in an antioxidant intervention study.