Background/purpose: The aims of this study were to investigate the clinical and immunohistochemical events of psoriatic plaques during photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA). Methods: Twelve psoriatic patients were recruited for this study. Four of them dropped out because of pain during treatment. The effect of PDT was evaluated in the remaining eight. One plaque was selected in each patient and treated once weekly with PDT 10–30 J/cm2 two to five times. It was evaluated by using the scale, erythema and induration (SEI) index (maximal score per patient=9). Pain during treatment was assessed by a visual analogue scale (VAS), ranging from 0 to 10. Skin biopsies were taken before treatment, after two treatments and after completion of treatment, and were evaluated by immunohistochemistry. Results: Median SEI scores were significantly reduced from 7 (range 5–9) before to 1.5 (range 0–3) following treatment (P<0.0001). The median pain during PDT was 7. The number of vessels in the subpapillary dermis, identified by antibodies against Factor VIII and endoglin, increased during and/or after treatment in six of eight patients. Before treatment, the epidermal growth factor (EGF) receptor was displayed throughout the epidermis, keratin 16 suprabasally, involucrin from the stratum granulosum to the lower spinous layers and filaggrin in stratum granulosum with focal absence. There was a moderate dermal infiltrate of CD4+ cells and a sparse one of CD8+. Following treatment, the EGF receptor was still displayed throughout the epidermis in seven of eight specimens. Cytokeratin 16 expression decreased markedly. Involucrin was not seen as deep in the spinous layers as before PDT. Filaggrin was expressed throughout the stratum granulosum and often weakly in the upper stratum spinosum. The number of CD4+ and CD8+ dermal cells decreased. Conclusion: PDT improved psoriasis and induced dermal neovascularization. Although a good clinical response was seen in most of our patients, the high frequency of discomfort during treatment limits the usefulness of ALA-PDT for psoriasis. The mechanism of the neovascularization is unknown. It may be owing to an indirect effect of PDT on the microvasculature and immune system or recovery phenomena.