Topical methyl aminolevulinate (MAL) is currently under study for the treatment of actinic keratoses. This approach involves topical application of MAL to the lesion to be exposed to light as well as a few millimetres of adjacent normal skin. We studied the effects of whole-body white light exposure following topical application of MAL to the entire back of hairless mice chronically exposed to UV radiation. Groups of mice were exposed to UV from FS20 lamps. One group of mice was treated weekly with 8% topical MAL followed 2 h later by suberythematous exposure to 1.2 J/cm(2) of light from a slide projector. MAL followed by light induced a significant delay in the time of appearance of the first tumour as compared to mice exposed only to UV ( P<0.0001). After 26 weeks of UV exposure large tumours (>/=4 mm) were present in 14 mice in the UV group as compared to only one mouse in the UV-MAL group. In mice treated on one side with MAL and the other side with vehicle, the delay in the appearance of tumour was only observed on the side treated with MAL, suggesting that a local rather than systemic effect was responsible for this phenomenon. In vivo fluorescence spectroscopy and quantitative fluorescence microscopy showed that there was a preferential accumulation of protoporphyrin IX in tumours as compared to adjacent UV-exposed skin and normal skin at the time of light exposure. In conclusion, topical MAL followed by light under suberythematous conditions delayed the appearance of UV-induced skin tumours without increasing mortality or morbidity, and thus acted in a prophylactic manner.