Previous study showed that the cosmetic ingredient chemical azulene and its derivative gauiazulene exhibited photomutagenicity four- to five-fold higher than spontaneous mutation in Salmonella typhimurium TA102. In this study, phototoxicity including photogenotoxicity of azulene in human Jurkat T-cells is reported. When the cell suspensions are irradiated by light (UVA plus visible light) in the presence of azulene, an azulene dose-dependent cellular DNA damage is observed. At the highest azulene concentration of 50 microM, the average DNA fragmentation is 33 +/- 10%, determined by single cell gel electrophoresis (Comet assay). Cell viability assay using fluorescein diacetate indicates that the cells could endure the damage and remain viable. Further study revealed that the combination of light and azulene can cause single-strand cleavage on pure PhiX174 plasmid DNA in solution. Studies using scavengers reveal that singlet oxygen and free radicals are involved in causing DNA cleavage. This suggests that the photomutagenicity of azulene in S. typhimurium TA102 could be due to DNA fragmentation caused by the concurrent exposure to azulene and light.