BACKGROUND The authors conducted a study to evaluate fluoride released from fluoride varnishes that had been applied with two different protocols. Fluoride release information for these two approaches may allow clinicians to vary application intervals to better meet the needs of their patients. METHODS The authors painted enamel slabs from exfoliated primary molar teeth either in a single application (five samples) or three times within a single week (five samples) with fluoride varnish (Duraphat, Colgate-Palmolive, New York). The samples were immersed in buffered calcium phosphate solution (pH 6) to simulate the oral environment; the amount of fluoride released was measured during a span of six months. RESULTS The total release of fluoride was significantly higher in the three-application regimen (34.9 micromoles) than in the single application (23.7 micromol). The rate of release was slower using the three-application regimen. Thus, applying fluoride-release varnish three times in a single week produced greater and longer release of fluoride than did one application. CONCLUSIONS Massed application of fluoride varnish during a single period during the year may be as effective as spaced single applications. This method can be a good alternative to delivering fluoride varnish to high-caries-risk patients who are mobile or difficult to recall.