Abstract Afloqualone (AQ) is an oral muscle relaxant and evokes ultraviolet A (UVA)-induced photosensitivity dermatitis as a side effect. Histologic observations of the skin eruption suggest that AQ photosensitivity is mediated not only by phototoxic but also by photoallergic mechanisms. To address the immunological mechanisms of AQ photosensitivity, we examined the immunogenicity of AQ-photomodified epidermal cells in mice. Afloqualone was covalently coupled with bovine serum albumin by irradiation with UVA but not UVB. Because of this ability of AQ to photobind to protein, murine epidermal cells were easily modified with AQ by exposure to UVA. Subcutaneous inoculation of AQ-photomodified epidermal cells successfully induced an antigen-specific delayed-type hypersensi-tivity in mice. These findings suggest that AQ-photoderivatized epidermal cells are highly immunogenic and that photomodification of epidermal cells with AQ is an initial event to evoke AQ photosensitivity dermatitis.