This study investigates the optimal method of administrating 5-aminolevulinic acid (ALA) in the context of photodynamic therapy (PDT) by analyzing protoporphyrin-IX (Pp-IX) fluorescence in skin and tongue tumor tissues. For skin tumor, Pp-IX intensities in nude mouse skin cancer were measured after topical application of three photosensitizers: ALA, ALA-methyl or ALA-hexyl derivatives. The combined effects of ultrasound and/or depilation cream were also examined. For the tongue tumor, Pp-IX intensities in mouse tongue cancer were compared with those in the normal tongue after intraperitoneal, oral or topical administration of ALA. The results showed the effects of a combination of depilation cream in all photosensitizers in the skin tumor. Application of hexyl derivative in combination with ultrasound or depilation cream showed higher Pp-IX concentration in the tumor tissue. Maximum Pp-IX accumulation in the tongue tumor tissue was seen at 5 It after oral administration of ALA. In contrast, the topical administration of 20% ALA cream showed lowest Pp-IX accumulation in the tongue tumor throughout the experiments. (C) 2002 Elsevier Science B.V. All rights reserved.