The psoralens are photoactivated plant biosynthetic compounds which are found in several plant families, including common fruits and vegetables. Synthetic forms of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) are extensively used in skin chemotherapy in combination with long-wave ultraviolet radiation (PUVA). Side effects of PUVA therapy are not, however, desirable, and this therapy has been linked with increased incidence of skin cancer in humans. The psoralens are known to be carcinogenic, mutagenic and teratogenic, and to cause photodermatitis. The main objective of this study was to document the effect of PUVA on the epidermis of rats. Female Wistar rats were administered dietary bergapten and/or xanthotoxin (0-200 mg/kg body) and exposed to UVA radiation (45 min./day) for four weeks. At the end of the four-week period the rats were sacrificed; skin samples were taken from the ears and the top part of the tail and fixed for examination by Scanning Electron Microscopy. The animals subjected to PUVA had significantly smaller scales on the tail epidermis (mean scale size for the control 926 mu vs. 725 to 805 mu for the psoralen treatment groups. The rats that received dietary psoralens also had significantly less hair on the ears compared with the control animals (mean number of hairs per millimeter over the ear edge for the control 54.9 vs. 2.00 to 10.7 for the treatment groups). The two compounds were synergistic in their ability to reduce scale size on the tail epidermis.