This study evaluated the effect of an alternate delivery system for chlorhexidine on salivary levels of mutans streptococci (MS) and other selected oral bacteria. On the basis of salivary MS levels > or = 10(4) CFU/ml, 22 subjects were enrolled. All caries lesions were restored prior to treatment. Two pretreatment paraffin-stimulated saliva samples were obtained for culturing at least 1 week apart. Complete-arch vacuum-adapted mouthguards were individually fabricated and coated internally with a 3% w/v chlorhexidine varnish. Mouthguards were worn for an average of 7 h/night for 7 nights. Saliva samples were obtained immediately after treatment and 1 and 3 months later. There was no significant change in levels of any of the monitored bacteria between the two pretreatment samples. A significant and specific reduction in salivary MS levels was observed in the three after-treatment samples as compared with baseline values (p < 0.001, p < 0.001, p < 0.05, respectively). The levels of Actinomyces viscosus were also measured, and there was a significant reduction immediately after treatment (p < 0.05), a return to baseline values at 1 month, and a significant increase above baseline values at 3 months, (p < 0.001). There was no significant change in saliva volume, in total numbers of facultatively anaerobic bacteria, or in levels of lactobacilli or Streptococcus sanguis. This treatment system is capable of significant and specific suppression of MS levels for up to 3 months without retreatment.