To demonstrate the specificity of cellular interaction in the spontaneous aggregation of Streptococcus mitis ATCC 903 the inhibitory effect of various sugars was studied. More than 90% inhibition was recorded in 0.1 M concentrations of D-glucosamine, D-galactosamine and D-mannosamine. A reduction of the inhibition by more than 50% was observed when the N-acetylated derivatives of the hexosamines were tested. Polymers containing hexosamines such as hyaluronic acid, heparin and fetuin were potent inhibitors, in contrast to dextrans of different molecular weights. Inhibition was less than 20% in lactose, melibiose, cellobiose, methyl beta-D-galactopyranoside and a number of other sugars tested in 0.1 M concentration. The bacteria retained their ability to aggregate after removal of the inhibitory sugars by washing in phosphate buffer. These findings support the hypothesis that the specific nature of the spontaneous aggregation of S.mitis ATCC 903 depends on a lectin-ligand type interaction.