OBJECTIVE The objective of this in vitro study was to compare two 5% sodium fluoride varnishes, each containing different sources of calcium and phosphate, for their ability to deliver fluoride into treated sound tooth enamel and adjacent, but untreated demineralized enamel. METHODS Six sets of 12 bovine enamel cores were mounted in plexiglass rods and the exposed surfaces were polished. Synthetic lesions were formed in the surface of three sets by soaking in thickened, pH 5.0, 1M lactic acid, 50% saturated with calcium hydroxyapatite. A fluoride varnish containing tri-calcium phosphate (TCP) was applied to one set of sound enamel cores, and a second, delivering amorphous calcium phosphate (ACP), was applied to another. A third set of sound enamel cores was water-treated. Each treated sound core was paired with an untreated lesioned core, and the pairs were soaked in artificial saliva for 24 hours at 37 degrees C. The treated cores, but not their lesioned counterparts, were initially soaked in 1.0 N KOH saturated with calcium phosphate for 18 hours. Each core was separately etched with 1.0 N perchloric acid for exactly 15 seconds, and fluoride measured by an ion-sensitive electrode after neutralizing with NaOH and buffering in TISAB II. The amount of calcium extracted was also determined by atomic absorption spectrophotometry as a measure of etch depth. RESULTS Fluoride uptake average was 1677 +/- 193 ppm, 455 + 38 ppm, and 44 +/- 5 ppm for the sound enamel cores treated with ACP varnish, TCP varnish, and water treatment, respectively. Fluoride uptake into the demineralized enamel averaged 5567 +/- 460 ppm, 2126 +/-126 ppm, and 49 -/+ 4 ppm for demineralized enamel paired with the sound cores treated with ACP varnish, TCP varnish, and water, respectively. The differences between the ACP varnish, the TCP varnish, and the water treatments were statistically significant (p < 0.05). CONCLUSIONS The ACP varnish formulation delivers statistically significantly more fluoride to both intact and demineralized enamel than the formulation containing TCP.