Two hypotheses have been put forward to explain the formation of photoallergens. One is that the photosensitizer is a photohapten that binds covalently to a carrier protein via the formation of free radicals resulting from ultraviolet (UV) irradiation. Thus, photohaptens are virtually the same as ordinary haptens, except for the fact that they require UV irradiation for covalent coupling with protein. Another theory suggests that the photosensitizer is a prohapten, which is converted to the complete hapten by UV irradiation. Our study suggested that the vast majority of clinically photoallergic chemicals are photohaptens rather than prohaptens. Because of the ability of photohaptens to photobind to protein, cells are easily photomodified with a photohapten by exposure to UV. Ultraviolet A light (UVA) includes the action spectrum of this photoderivatization, because protein and cells are photocoupled with photohaptenic substances by irradiation with UVA but not with UVB. The photohapten-modified cells are capable of immunizing and eliciting in vivo immune responses and in vitro proliferation of sensitized T cells. Two major diseases are caused by photohaptens: photoallergic contact dermatitis and drug photoallergy. The former is evoked by skin application of a photohapten followed by UVA irradiation, and the latter disease is induced by oral administration of a photohapten plus UVA exposure. In these disorders, the causative photohaptens are bound to MHC class II molecules/self peptides on Langerhans cells upon exposure to UVA. These photomodified Langerhans cells sensitize and elicit antigen-specific T cells that mediate the photodermatitis.