Fourteen 8-hydroxyquinolines were tested for antiplaque activity by measuring their minimum inhibitory concentrations [MIC (M)] against Streptococcus mutans No. 6715. Linear regression analysis was conducted with the MIC (M) values and hydrophobic (log P), electronic (beta, pKaOH, pKaN), and steric [molar refractivity (MR), molecular weight (mol wt)] parameters. The best correlation (r2 = 0.90) was obtained with MR, log P, and beta. The smaller the steric contribution of the 5-substituent, the more active the compound. The parent 8-hydroxyquinoline was the most active. The negative contribution toward activity by 5-substituents larger than hydrogen can be overcome by the positive contributions of groups that are lipophilic and electron withdrawing; for example, the 5-chloro derivative is as active as the parent 8-hydroxyquinolines.