Background: Virtually all plants and animals protect themselves from the sun using vitamins C and E. Objective: The purpose of this study was to see if a combination of topical vitamins C and E is better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone. Methods: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% ⍺-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5× minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers. Results: The combination of 15% L-ascorbic acid and 1% ⍺-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% ⍺-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation. Conclusion: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging. (J Am Acad Dermatol 2003;48:866-74.)