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Objective: We aimed to compare the effect of sodium fluoride and chlorhexidine on salivary levels of mutans streptococci (MS), in a double-blind, randomized clinical trial., Methods: Thirty-five healthy volunteers, aged 4-8 years, with at least one active carious lesion and no previous history of allergies were selected to participate in the study. A gel formulation containing either 1.23% sodium fluoride or 1% chlorhexidine was topically administered to the dentition every 24 h for 6 consecutive days. Salivary MS levels were measured at baseline (D1) and on the 6th (D6), 15th (D15), and 30th (D30) days. For microbiological analysis, Mitis Salivarius-Bacitracin agar medium was used., Results: Difference between treatments was only verified on D6. On the last day of treatment 1% chlorhexidine gel was significantly more effective than fluoride (P = 0.0000). The use of sodium fluoride did not cause a statistically significant variation in salivary MS levels throughout the duration of the study. Following treatment, a subsequent increase in MS counts between D6 and D15 (P = 0.0001) was observed with chlorhexidine., Conclusion: A 6-day treatment with a 1% chlorhexidine gel was effective in reducing salivary MS; there was a significant MS increase once treatment was suspended. The use of 1.23% sodium fluoride under the same regimen was not able to reduce salivary MS levels. Our results suggest repeated treatment with 1% chlorhexidine as a means for maintaining low salivary MS levels in children with dental caries.