Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.