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Notes: Background  Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans.Objectives  The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment.Patients/methods  Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580–650 nm) and fluence rates of 30 or 45 mW cm−2, and two groups with broad filter (580–690 nm) and fluence rates of 50 or 75 mW cm−2. The total cumulative light dose was 100 J cm−2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks.Results  Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photobleaching dose (1/e) was found to be related to fluence rate, ranging from 4·5 ± 1·0 J cm−2 at 30 mW cm−2, to 7·3 ± 0·7 J cm−2 at 75 mW cm−2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm−2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm−2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm−2.Conclusions  Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm−2) seems preferable when performing PDT of AK using noncoherent light sources.