Attempts to develop PDT for eradication of Helicobacter infection have only been successful in vitro. We have investigated the effect of topical sensitization (except ALA) of Helicobacter mustelae on explanted ferret gastric mucosa using one of five sensitizers (methylene blue (MB), toluidine blue O (TBO), phthalocyanine, haematoporphyrin derivative and 5-aminolavulinic acid), followed by irradiation with an appropriately tuned copper vapour pumped dye laser. A 90% reduction in counts of bacteria sensitized with 0.75 mg TBO kg-1 were seen after irradiation with 200 J cm-2. Concentrations of MB of 0.75 mg kg-1 and 7.5 mg kg-1 were not toxic to H. mustelae, but the further addition of 20 J cm-2 laser light reduced colony counts by more than 99%. MB at a concentration of 75 mg kg-1 exhibited significant dark toxicity towards H. mustelae, but further addition of 20 J cm-2 laser light resulted in near eradication of all colonies. The remaining three compounds were ineffective. Finally, we studied the microscopic fluorescence distribution of MB (7.5 mg kg-1) on ferret gastric mucosa after topical administration. Fluorescence was greatest in the superficial mucosal layer, upon which lies the bacteria. However, from experiments on rats, the energy required to kill the sensitized bacteria was insufficient to damage the underlying mucosa. We conclude that Helicobacter can be killed on host mucosal epithelium following topical administration of MB and subsequent exposure to laser light.