The effect of multiple treatments with chlorhexidine mouth guards on salivary levels of mutans streptococci (MS) was studied. Eleven subjects with salivary MS > or = 10(5) CFU/ml were randomly assigned to an experimental or control group. Complete-arch mouth guards were coated internally with one of two ethylcellulose varnishes, one containing 30% dry w/w chlorhexidine and one containing no chlorhexidine. Subjects wore the mouth guards up to four times, each time for 7 consecutive nights while sleeping, with at least a 1-week break between treatment weeks. Subjects in the control group subsequently crossed over and also wore the chlorhexidine-containing mouth guards. Each of the week-long mouth guard sessions resulted in a reduction in mean salivary MS levels as follows (log10 CFU/ml): for the experimental group, -1.0, -0.9, -1.0 and -1.2, and for the crossover group, -1.7, -0.6, -0.5 and -0.6. Salivary MS levels were (mean +/- SD) 6.4 +/- 0.5 at baseline and 3.8 +/- 0.5 after the last mouth guard session for the experimental group and 6.0 +/- 0.5 and 4.3 +/- 0.7, respectively, for the crossover group. For the control group, there was no significant change in MS levels.