A mutant (UAB108) derived from Streptococcus mutans UAB66, a spectinomycin-resistant (Spc(r)) isolate of strain 6715, inhibited plaque formation when grown with strain 6715 in a sucrose medium and also inhibited caries formation in gnotobiotic rats infected with both strain UAB108 and 6715. A substance obtained from UAB108 culture supernatant fluid after ethanol precipitation and DEAE-cellulose treatment, designated glucan 108, inhibited S. mutans 6715 virulence and was shown to be a water-soluble glucan. In the presence of sucrose and increasing concentrations of glucan 108, the activity of glucosyltransferase (GTase) preparation from S. mutans 6715 to synthesize adhesive water-insoluble glucan (ad-WIG) was inhibited and the activity to synthesize non-ad-WIG was stimulated. Glucan 108 similarly inhibited sucrose-dependent adherence of heat-treated cells, was a poor inducer of cell aggregation, and inhibited S. mutans 6715-induced dental caries in gnotobiotic rats. In the presence of GTase, glucan 108, and sucrose, the glucose moiety of sucrose was found to be incorporated into glucan 108, and most of this glucose-incorporated glucan 108 was found in the non-ad-WIG fraction. The mode of inhibition of plaque formation by S. mutans 6715 appears to involve a shift from ad-WIG to non-ad-WIG formation. The water-soluble glucan 108 was found to have an approximate molecular weight of 2 x 106 and was hydrolyzed by fungal dextranase to yield glucans with an average molecular weight of about 1.2 x 104. This glucan (designated glucan 12k) was further hydrolyzed by bacterial dextranase to yield smaller glucans and oligosaccharides, but was refractile to α(1→3) glucanase. These results suggest that glucan 108 is a branched α(1→6) glucan, and it is proposed that UAB108 is defective in its ability to polymerize glucan 12k with α(1→3)-linked glucosyl residues.