Among the anticaries benefits of fluorides is the remineralization of incipient carious lesions. There is increasingly convincing evidence that low-potency fluoride agents applied frequently are effective in remineralizing early carious lesions. This study of in vivo remineralization used an intraoral appliance with demineralized enamel slabs mounted in the appliance and an innovative method of fluoride delivery, the fluoride-releasing device, which releases a controlled amount of fluoride (0.3 mg fluoride every 24 hours) on exposure to saliva. After control and treatment periods of 7 and 30 days, the enamel specimens were removed from the appliance and evaluated for microhardness, acid resistance, and fluoride uptake. The treated specimens significantly exceeded the values of their corresponding controls in all parameters measured, indicating that considerable remineralization of the treated enamel had occurred at both 7 and 30 days. Although the longer period of treatment produced greater results, considerable effects were observed after 7 days. This model system provided for an in vivo environment to study the effects of treatment of the FRD and allowed for subsequent recovery of the enamel specimens for evaluation. The results of this study are encouraging with respect to the efficacy of a fluoride-releasing device but indicate that subsequent clinical testing of the effects of FRDs on incipient carious lesions in the natural dentition of human subjects is necessary.