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Notes: Summary Background Photodynamic therapy (PDT) is a local treatment modality with increasing indications for various malignant and non malignant diseases. The treatment parameters have not yet been optimized as there is a need for a better understanding of the process. The skin is an important target and serves as a good model for monitoring and evaluating the interaction of light with biological tissue. Objectives The tissue perfusion and the temperature of basal cell carcinomas were measured in connection with PDT in order to investigate the biological mechanisms involved. Methods An infrared camera was used during the treatment to measure skin temperature and a laser Doppler perfusion imaging device was used to image the superficial perfusion before and after treatment. Six hours after topical application of 5-aminolaevulinic acid (ALA) or methyl esterified ALA (ALA–ME), 38 basal cell carcinomas were treated using light from a diode laser at 633 nm. Results In the lesions, the perfusion immediately after PDT was similar to that before PDT. One hour after the treatment the perfusion in the lesion was increased 50% compared with before PDT. However, in the skin surrounding the lesions the perfusion was doubled immediately after PDT and was still increasing 1 h after treatment. A temperature increase in the lesions of about 1–3 °C was observed for light fluence rates of 100–150 mW cm−2. In all patients treated, a diffuse temperature increase was visible outside the lesions. In some of the patients, the outlines of the blood vessels surrounding the treated lesions became visible in the thermal images. Measurements of temperature on healthy volunteers not administered photosensitizer, but illuminated with light of the same fluence rate, showed a similar increase in temperature in the illuminated spots. However, no temperature increase was observed outside the illuminated area. No statistically significant differences were found between the measurements on patients treated with ALA and ALA–ME. Conclusions The increased perfusion in the area surrounding the lesions after PDT, as seen by perfusion and temperature measurements, is the result of an inflammatory reaction to the PDT process. However, directly after PDT the perfusion in the lesions was the same as before irradiation. The combination of these observations suggests the presence of local blood stasis during and immediately after the treatment. The temperature measurements showed that the increased temperature was well below the temperature limit of hyperthermal damage. Furthermore, the measurements indicate that the increase in temperature was primarily a consequence of the heat absorbed in the tissue.