Recently, medium-dose UVA1 phototherapy (50 J/cm2) has been introduced as an effective treatment for severe atopic dermatitis (AD). In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement in skin status in patients with AD, biopsy specimens from ten patients before and after treatment were analysed immunohistochemically for features of apoptosis. We sought to determine the extent to which UVA1 irradiation was able to modulate the balance between p53 and bcl-2 expression in vivo using monoclonal antibodies labelling these proteins. As compared with lesional skin of patients with AD before UVA1 irradiation, the number of dermal cells, apparently lymphocytes, that were positive for p53 had significantly increased after treatment and, in addition, some basal keratinocytes showed slight positive staining for p53. An increased expression of the bcl-2 gene before treatment in predominately dermal lymphocytes was significantly downregulated by UVA1 therapy. The increase in p53+ cells and the decrease in bcl-2+ cells were closely linked to a significant reduction in dermal T cells (CD3+) and a substantial clinical improvement in skin condition. In summary, medium-dose UVA1 irradiation led to a marked modulation of the expression of p53 and bcl-2, and this plays a key role in regulating UVA1-induced apoptosis.