Dematologists estimate that 15% of the cases of skin allergy diagnosed in dermatology clinics involve plant-derived toxins and photosensitizers. Our studies have clearly established the presence of a large group of novel allergens that can bring about severe delayed hypersensitivity reactions and immunological inflammations. In this competing continuation, we are requesting continuing support for our collaborative phytochemical and dermatoxicological investigations of novel phytoallergens and photosensitizers. We specifically propose to: (i) expand our phytochemical investigations of new and unstudied allergenic plants from arid and tropical/subtropical zones of the United States and Mexico; (ii) elucidate the structures of novel contact allergens and photoallergens and investigate the molecular mechanisms of action, toxicity and potential medicinal value of these compounds, (iii0 determine the dermatological role of urocanic acid, an important skin metabolite that interacts with photoallergens to either promote or prevent allergic reactions; and (iv) investigate the mutagenic and/or carcinogenic potential of potent contact allergens that cleave DNA. The knowledge of molecular structure, immunological response and dermatotoxicity of contact allergens will provide dermatologists with fundamental information for diaagnosing, and treating natural product- induced allergies and photosensitizations.