We investigated the effect of the potentially carcinogenic psoralen plus UVA radiation (PUVA) therapy on the expression of p53 in skin of psoriatic patients. p53 antibodies DO7 and Pab240, antibodies against PCNA and Ki67 and the avidin-biotin immunoperoxidase complex method were used in the immunohistochemical staining of biopsy samples from non-lesional and lesional skin of 23 patients who received either trioxsalen bath PUVA or oral 8-methoxypsoralen PUVA. Biopsies were taken before and after a PUVA course. A modest expression of p53 was seen in psoriatic lesions in 17/21 patients before any treatment, probably as a physiological reaction to the hyperproliferation. Both p53 and the proliferation markers Ki67 and PCNA followed the same pattern, being more frequent in psoriatic lesions than in non-lesional skin. Exposure to PUVA induced an increase in p53 expression in non-lesional skin in 14/19 patients, putatively as a response to DNA damage caused by PUVA. In psoriatic lesions about half of the patients showed increased and half decreased expression of p53. The latter finding might be explained by decreased proliferation activity of the healing epidermis. In conclusion, p53 nuclear positivity in non-lesional skin after PUVA treatment is likely to be induced by DNA damage caused by PUVA, while in psoriatic lesions it could be a result of the combined effect of decreasing epidermal proliferation and DNA-damage.