The photoprotective properties of furocoumarin plus UVA-induced epidermal melanogenesis were assessed in hairless mice. The ear and dorsal surfaces were topically treated with 6,4,4'-trimethylangelicin (TMA), 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) or psoralen and exposed to UVA for 12 consecutive week-days. The TMA treatment induced intense tanning whereas modest tanning was seen with the other compounds. Seven days after the last treatment, the mice were challenged with a DNA damaging dose of UV radiation. Single strand breaks (SSB) in epidermal DNA were assessed by alkaline elution. Photoprotection was assessed by comparing SSB in furocoumarin-treated mice with control mice (vehicle plus UVA and also no treatment). No photoprotection was seen, with any compound, in dorsal epidermis despite intense pigmentation induced by TMA. Modest photoprotection with all compounds was seen in ear epidermis that was independent of the level of pigmentation. These data show that induced melanogenesis is not always associated, with photoprotection.