Although quinolone antibacterial agents have both phototoxicity and photoallergenicity, the latter's potency has been poorly investigated compared with the former's. Some of the photoallergic chemicals serve as photohaptens, which lead to T-cell-mediated immune reactions after photobinding to protein by UVA radiation. We examined the photohaptenic potential of fluoroquinolones, including lomefloxacin (LFLX), ciplofloxacin, norfloxacin, ofloxacin, levofloxacin, fleroxacin, enoxacin and sparfloxacin (SPFX). The absorption spectra of the quinolones were altered by UVA irradiation, with an exception of SPFX that seems to be photostable toward UVA. Bovine serum albumin and murine epidermal cells were coupled with these fluoroquinolones other than SPFX by exposure to UVA. Subcutaneous inoculation of fluoroquinolone-photomodified epidermal cells induced and elicited a delayed-type hypersensitivity reaction in mice. However, epidermal cells incubated with LFLX without UVA exposure also induced and elicited a significant hypersensitivity reaction to a lesser degree than LFLX-photomodified epidermal cells. Furthermore, there was cross-reactivity between LFLX-photomodified epidermal cells and simply LFLX-incubated cells. This suggests that cells can be weakly modified with LFLX even in the dark and that UVA irradiation promotes this modification. Our study demonstrated that fluoroquinolones have photohaptenic properties to which their photoallergenicity is probably ascribed.