The main form of folate in human plasma is 5-methyltetrahydrofolate (5MTHF). The observation that folate in human serum is photosensitive supports the hypothesis that humans developed dark skin in high ultraviolet fluences areas in order to protect folate in the blood from UV radiation. However, folates alone are quite photostable. Therefore, in this study, we examined for the first time the photodegradation of 5MTHF in the presence of the endogenous photosensitizer uroporphyrin (Uro), which is sometimes present in low concentration in human serum, under UV and near-UV light exposure. We found strong indications that while 5MTHF alone is rather photostable, it is degraded quickly in the presence of Uro. Using deuterium oxide (D(2)O) as an enhancer of the lifetime of singlet oxygen and the singlet oxygen sensor green reagent (SOSG) as a scavenger of singlet oxygen, we have found that the photodegradation most likely proceeds via a type II photosensitization. Our results show that singlet oxygen is likely to be the main intermediate in the photodegradation of 5MTHF mediated by Uro. Our findings may be useful for further studies the evolution of human skin colours.