Phototoxic reactions result from direct cellular damage produced by the photoproducts, provided enough of the chemical and radiation are present. No immunologic mechanisms are involved in phototoxic reactions, so they can manifest themselves during an initial exposure. Phytophotodermatitis caused by bergamot oil, parsley, celery, dates, and other plants containing the furocoumarins is a classic example of phototoxic reaction (Figure 1). At a molecular level, most phototoxic reactions (eg, in the case of acriflavine, porphyrins, chlorothiazide, tetracyclines, nonsteroidal anti-inflammatory agents, quinolones, and certain dyes, such as methylene blue) develop in the presence of oxygen, in which free radicals resulting from photo-oxidation and peroxidation processes cause injury to cell nuclei, cytoplasm, and cellular membrane components. Phototoxicity reactions to psoralens, although rarely requiring molecular oxygen, are for the most part oxygen independent. In those cases, UV-A–induced covalent binding (formation of cyclobutane dimers) between the chemical and the molecules of DNA occurs. Similar dimers are formed between chlorpromazine and RNA molecules.13,20 The factors that strongly influence the incidence, intensity, and clinical features of phototoxic reactions include (1) the nature, concentration, absorption, and pharmacokinetics of the drug; (2) quantity and spectrum of radiant energy; and (3) factors related to the skin thickness of the stratum corneum, quantity of melanin, temperature, and humidity.