Helicobacter pylori can colonize the stomachs of Mongolian gerbils and subsequently induce penetrating ulcers five months later. Using this gerbil model, the effects of both combined treatment with omeprazole and clarithromycin, as well as treatment with each drug separately, on the healing of H. pylori-induced gastric ulcers, and the effects of the cessation of the drug treatment on healed ulcers were examined. Beginning five months after H. pylori (NCTC11637) inoculation, omeprazole (four weeks), clarithromycin (two weeks), their combination, or the vehicle was orally administered once daily. These drugs, in combination or separately, markedly enhanced ulcer healing and lowered the increased myeloperoxidase (MPO) activity. While omeprazole had no effect on viable H. pylori, clarithromycin and the drug combination significantly reduced viable H. pylori. The degree of bacterial eradication was much higher in the case of the drug combination compared to clarithromycin alone. Four months after cessation of the treatment, visible ulcers, hypertrophic gastritis and increased MPO activity were found in the control animals (all H. pylori-positive). Nonetheless, only one of the eight gerbils subjected to the drug combination developed a small ulcer, although no hypertrophic gastritis was exhibited. It is concluded that: (1) the gerbil model of H. pylori infection is useful for the study of ulcer healing; (2) combined treatment with omeprazole and clarithromycin enhances the ulcer healing in infected gerbils; and (3) healed ulcers do not relapse, despite cessation of the drug treatment.