OBJECTIVE To compare fluoride uptake by enamel after applying 1.23% acidulated phosphate fluoride gel to human tooth enamel topically (n = 12) or with combined dielectrophoresis and AC electroosmosis (DEP/ACE) at frequencies of 10, 400 and 5,000 Hz (n = 12) for 20 minutes. METHODS DEP/ACE induced nonuniform electrical fields with three alternating current frequencies to polarize, orient, and motivate fluoride particles. Fluoride concentrations were measured at various enamel depths using wavelength dispersive spectrometry. Data were analyzed by ANOVA/Student-Newman-Keuls post hoc tests (P < or = 0.05). RESULTS Fluoride concentrations in the diffusion group were significantly higher than baseline readings at 10, 20 and 50 microm depths. Fluoride concentrations in DEP/ACE-treated teeth were significantly higher than the diffusion group at 10, 20, 50, 100, 200 and 300 microm (ANOVA/Student-Newman-Keuls post hoc, P < 0.05). Fluoride uptake with DEP/ACE was substantially higher than diffusion at 10, 20, 50, 100, 200 and 300 microm depths (paired t test, P < 0.05). DEP/ACE transported fluoride up to 300 microm deep, whereas conventional fluoride application was comparatively ineffective beyond 20 microm depth (P < 0.05). Compared to passive diffusion, fluoride uptake in enamel was significantly higher in the DEP/ACE group at 10, 20, 50, 100, 200 and 300 microm depths (P < 0.05). DEP/ACE drove fluoride substantially deeper into human enamel with a difference in uptake 1,575 ppm higher than diffusion at 100 microm depth; 6 times higher at 50 microm depth; 5 times higher at 20 microm depth; and 7 times higher at 10 microm depth. Fluoride levels at 100 microm were equivalent to long-term prophylactic exposure.