The overall research objectives under this grant are directed to evaluate the beneficial and harmful effects of ultraviolet radiation in human skin with special emphasis on the photoreactive agents, furocoumarins (psoralens), used in the treatment of psoriasis, vitiligo, etc. The work summarized in this progress report included studies on: (1) The pharmacology of psoralens (absorption, metabolism, and structural properties of metabolites). (2) The mutagenic and lethal properties of certain bifunctional furocoumarins (interstrand crosslinking agents with DNA) such as psoralen, 8-methoxypsoralen, 5-methoxypsoralen, and mono-functional furocoumarins (single-strand conjugating agents with DNA) with the standard Ames test. (3) The data of a three-year study involving the relative effectiveness of three psoralens (8-methoxypsoralen, 4,5',8-trimethylpsoralen, and psoralen) in the repigmentation of 365 vitiligo patients were analyzed, and the results indicated that the photochemo-therapy of vitiligo with oral 8-MOP either alone (0.3 to 0.6 mg/kg) or in combination with TMP (0.3 mg/kg 8-MOP plus 0.6 mg/kg TMP) can be an effective treatment given patient compliance and regular long-term follow up. In addition, long-term actinic and carcinogenic effects of this therapy and the frequency of subclinical thyroid disease including hypo- and hyper-thyroidism have been studied in vitiligo patients. (4) Another pigmentary abnormality aggravated by sunlight includes melasma, a disfigurement condition, which is not well understood. Using histochemical, light microscopic, and electron microscopic techniques, a comparative study of lesional and control skin biopsies involving 14 patients with melasma was initiated. The study also summarized the results of two double-blind clinical trials involving 221 Hispanic patients using various depigmenting formulations in the treatment of melasma. The data revealed that melasma can be best treated with 4% hydroquinone or 2% hydroquinone in combination with 0.05 to 0.1% retinoic acid. (5) Other disease conditions that are aggravated by sunlight and studied for the mechanisms of skin photosensitization reactions included various porphyrias and solar urticaria.