Clinical reports indicate that the fluoroquinolone group of antibiotics can induce cutaneous photosensitivity reactions. In the present study, phototoxicity and photoallergenicity of quinolones including nalidixic acid (NA) norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX), and tosufloxacin (TFLX) were experimentally examined in an in vivo system using the guinea pig. Phototoxicity of all quinolones tested was demonstrated after a single, oral administration of the drugs and subsequent exposure to long-wave ultraviolet (UVA) at a dose of 30 J/cm2. The phototoxic potencies were: ENX, LFLX > OFLX > NA, TFLX > NFLX, CPFX. Photoallergic reaction was also induced to LFLX and NA by pretreatment with cyclophosphamide, an immunoadjuvant. No cross-reactions in photoallergy were observed among quinolones. The photo-ingestion test was positive in photoallergically sensitized animals, while the photopatch test was negative. This is the first report which demonstrated experimentally the photoallergenicity of quinolones. Clinical features of the photosensitivity due to quinolones can be explained by the results of the present experiments.