OBJECTIVE Intraoral fluoride-releasing (IFR) devices provide elevated levels of fluoride in the mouth for extended periods of time. However, retention and protection of the devices have posed major challenges for clinical applications. The objectives of this study were to develop new methods for retaining and protecting IFR devices in the mouth and to assess their effects on salivary fluoride levels and distribution in adolescents. METHODS Four different IFR systems (combinations of an IFR device and its retainer) were evaluated in four groups of 10 adolescents each, 12-15 years of age, for a period of six months. Each child wore two IFR systems of a given type affixed to the buccal surface of each permanent maxillary first molar. Unstimulated saliva samples were collected at each clinical examination and analyzed for fluoride. RESULTS A significant increase in salivary fluoride concentration from a baseline mean of 0.07-0.69 microgram/mL was observed on day 14 postinsertion. IFR system retention was 85% after 6 months and, of the systems retained, 100% were functional. CONCLUSIONS These findings suggest that IFR devices can be successfully protected and retained in the mouth for prolonged periods of time.