The aim of this study was to determine the fluoride release from toothpicks and dental flosses in vitro and in vivo, and to evaluate various approximal administration methods. In vitro, a total of 23 commercially available toothpicks and dental flosses and 3 prototypes impregnated with sodium fluoride (NaF), amine fluoride (AmF) or a combination of these two were tested. Fluoride release was determined for up to 24 h using an ion-specific electrode. A large variation was found between the products; most fluoride being released after 30 min. Generally speaking, toothpicks produced higher values than flosses. In vivo, the fluoride concentration in both treated and non-treated approximal areas was evaluated after using 2 different types of toothpicks and 4 dental flosses and after different application methods--such as a fluoride gel and fluoride solution. The mean fluoride concentration in oral fluid was up to 10 times higher at the treated sites than at the non-treated sites. Use of a fresh toothpick or a fresh piece of dental floss in each approximal space resulted in higher values compared with using one and the same toothpick/floss for the whole dentition. An interdental brush dipped in 0.2% NaF gel and a mouthrinse with 0.2% NaF resulted in elevated fluoride concentrations at the same level as when multiple toothpicks were used. To conclude, there are large variations in the fluoride release from various brands of fluoridated toothpicks and dental flosses. Treatment with a fluoridated toothpick or a dental floss can be expected to give elevated fluoride concentrations in the approximal area up to 60 min. Another interesting method for administering fluoride in the approximal area is to use an interdental brush dipped in fluoride gel.