The purpose of this investigation was to study the intra-oral effects of multiple daily applications of NaF lozenges upon acid-softened enamel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and subsequently mounted in a mandibular removable Hawley appliance. Control slabs were worn for seven days by eight adult male subjects who brushed their natural dentition daily with a fluoride-free dentifrice. Test slabs were exposed to one 0.55-mg NaF lozenge (0.25 mg F) 4x/day for seven days and the natural dentition brushed with a fluoride-free dentifrice. The efficacy of 0.25-mg F lozenges used 4x/day over that of a 1-mg F lozenge administered 1x/day was established by a pilot study with two subjects. Microhardness testing was performed after intra-oral exposure (IOE) and following immersion in 0.01 mol/L lactate buffer containing Ca and PO4 for 24 hrs at a pH of 4.0. Fluoride uptake was measured on separate control and test slabs after KOH wash and after acid-resistance-testing (ART). Recovery of microhardness following IOE was 40.9% for controls and 53.9% for treated slabs, while control slabs retained 1.3% resistance to ART, compared with 25.6% for test slabs. The F content of the control slabs was significantly less than that of lozenge-treated and lozenge-treated-ART slabs throughout the depth of the lesion. The F content of the lozenge-treated-ART slabs was significantly less than that of the lozenge-treated slabs only at the 0-5-microns depth.(ABSTRACT TRUNCATED AT 250 WORDS)