The percentage of Streptococcus mutans and Streptococcus sanguis in interproximal plaque following 5–10 daily applications of either an acidulated phosphate fluoride (APF) gel or a placebo gel was determined. Institutionalized boys, 14–16 years of age, residing in a rehabilitation center and who had detectable levels of S. mutans and S. sanguis in their plaque served as subjects. The APF gel increased the fluoride levels in the enamel surface from 1,889+403 to 3,284 ± 1,737 ppm, whereas the placebo gel had no effect on the enamel fluoride, i.e. approximately 1,950 ppm pre and post treatment. Six days after treatment, the percentage of S. mutans had decreased in 15 of 17 APF subjects but in only 4 of 10 placebo subjects. Six weeks after treatment, 13 of 17 APF subjects still had decreased percentages of S. mutans, whereas only 2 of 9 placebo subjects showed decreased levels. These differences were significant by χ2-analysis. S. mutans and S. sanguis each comprised about 5–7% of the plaque colony-forming units prior to treatment. Six days after APF treatment, S. mutans was reduced by about 75%, and remained at these low levels for at least 12 weeks. No change in S. mutans levels were seen in the placebo group. When the APF and placebo groups were compared using a paired t-test, a significant reduction in the S. mutans at 6 days post treatment was found. Fluoride or placebo treatment had no effect on plaque levels of S. sanguis. This study suggests that a topical APF gel may have a direct antibacterial effect on S. mutans.