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The purpose of this animal investigation was to determine whether the cariostatic effect of sodium fluoride can be enhanced by combining it with certain surfactants. The surfactants, Zonyl FSC and Lodyne S-110, were selected because they had been found to accelerate the rate of deposition of firmly-bound fluoride in vitro in enamel during enamel-fluoride interaction. Sixty male hamsters and 60 female rats, 21 days old, were placed on the high-sucrose diet 2000 and inoculated with Streptococcus mutans (strain #6715). Each set of animals was divided into six groups of 10 each. The groups received either distilled water, NaF, NaF with Lodyne S-110, NaF with Zonyl FSC, Lodyne S-110, or Zonyl FSC. The animals were scored for caries at the termination of the study. The caries findings in the hamster and the rat series closely paralleled each other. Animals receiving NaF with Zonyl FSC experienced the least decay (about 90% inhibition compared with about 65% for the NaF-alone group). A statistical evaluation showed significant interaction between Zonyl FSC and NaF. No effect on caries experience was seen from administration of Lodyne S-110.