To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamster's were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n = 26). PDT was performed (100mWcm(-2), 100Jcm(-2), continuously or fractionated, and 25 mW cm(-2), 100J cm(-2); continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20Jcm(-2) for 15 min. Prior to and up to 24 h after PDT tissue, pO(2) was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n = 36). Only high-dose PDT resulted in a significant decrease of pO(2), Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO(2). No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.