The initiation and prevention of xerostomia-related dental caries were studied using an in situ model. The morphology of induced carious lesions was compared with that of natural xerostomia-related dental caries. Both natural and induced xerostomia-related dental caries showed the same patterns of decay. Using the in situ model three preventive procedures were tested: neutral F gel applied every second day or weekly, and a daily rinse with a fluoride mouthwash for a period of six weeks. Application of fluoride gel or the use of the fluoride mouthrinse resulted in significant inhibition of the demineralization process. Of the procedures evaluated fluoride gel applied every second day was the most effective in preventing the onset of xerostomia-related dental caries.