A new therapy for the treatment of oral leukoplakia by 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) is presented. ALA, a precursor in the biosynthesis of haeme, induces the production of the endogenous photosensitizer protoporphyrin IX which can be used for PDT. Twelve patients, who had been suffering from leukoplakia of the oral mucosa for several years, were treated by ALA-mediated PDT. ALA was used as a topical photosensitizer and 20% ALA cream was applied to the leukoplakia lesion of the oral mucosa for two hours and then light activated at 630 nm, 100 mW/cm2 and 100 J/cm2. Five patients showed complete response to the treatment, four patients showed a partial response and in three patients treatment was unsuccessful. One patient with partial response was retreated, after which the lesion disappeared.