Photodynamic therapy (PDT) consists of the combination of photosensitizers absorbing light mainly in the red spectral region and irradiation with light of corresponding wavelengths. We analysed its effects on the cytokine secretion (IL-1 beta, TNF alpha, IL-6) of freshly isolated peripheral mononuclear cells from six patients with chronic plaque-stage psoriasis in comparison with PUVA. PUVA treatment resulted in a decreased production of all three cytokines, but most pronounced in the case of IL-6. PDT caused a similar change in the cytokine pattern, but its effectiveness was lower. In vivo fluorescence recordings were performed on psoriatic plaque lesions after topical application of the photosensitizer Photosan-3. Under irradiation, progressive photobleaching was noted with increasing radiation dosage. This is the first reported study of photochemical reactions using on-line fluorescence recordings during PDT of psoriatic lesions in vivo. Our results demonstrate the capacity of PDT to cause immunomodulatory effects similar to PUVA, thus indicating its potential application to the treatment of this common disease.