The aim of this double blind, cross-over, scanning electron microscopic (SEM) study was to compare the effect of topical application of 0.5% delmopinol HCl (aqueous solution) with placebo on early supragingival plaque formation on enamel specimens attached to a maxillary premolar. 3 subjects underwent 2x (placebo and delmopinol treatment, respectively) 7 treatment periods (1/2, 1, 2, 8, 24 hours; 3, 7 days) of undisturbed dental plaque accumulation, during which 2 ml of placebo and delmopinol HCl 0.5%, respectively, were applied topically to all teeth 2x daily. At the end of each period, the specimen was retrieved and processed for SEM. For the specimens obtained after 24 h or less, the number of visible micro-organisms was estimated. For the 3- and 7-day specimens, the area covered by plaque was calculated planimetrically. Large inter-individual differences were observed in the number of bacteria attaching during the first 24 h, with apparently no major differences between delmopinol and placebo. 1 subject showed a bacterial colonization predominated by curved rods throughout the first 8 h. Compared to placebo, the area of the specimens covered by plaque was reduced after 3 and 7 days of delmopinol use, with coccoid cells as the predominant morphotype. Plaque maturity, characterized by the appearance of corncob formations and high numbers of different morphotypes, was not observed on the delmopinol specimens, in contrast to the placebo specimens. The study shows that topical application of 0.5% delmopinol HCl delays and interferes with dental plaque maturation.