Background: Iron is a factor in skin photodamage, apparently by way of its participation in oxygen radical production. Certain topical iron chelators are photoprotective. Objective: Our purpose was to determine the level of topical photoprotection provided by the iron chelator 2-furildioxime (FDO) in combination with sunscreen in short- and long-term photoprotection models. Methods: Guinea pigs were treated topically with EDO, sunscreen, and a combination of the two and were then exposed to varying doses of UV radiation to determine the sun protection factor (SPF). Hairless mice were treated topically with FDO, sunscreen, and a combination of the two and then subjected to long-term, exposure to a suberythemal dose of UV radiation. The mice were evaluated for skin wrinkling and skin tumors. Results: In guinea pigs, topical FDO combined with sunscreen provided more than additive protection; 5% FDO alone provides approximately SPF 3, whereas 5% FDO combined with an SPF 4 sunscreen product yielded an SPF of more than 30. In hairless mice exposed long term to UV radiation, 5% FDO and sunscreen delayed tumor onset by a mean of 8 and 12 weeks, respectively. The combination of FDO and sunscreen delayed tumor onset by a mean of 58 weeks. A similar more than additive level of protection was observed for skin wrinkling. Conclusion: Topical FDO combined with sunscreen is a potent photoprotection system against both short- and long-term UV radiation exposure.