The main purpose of the present study was to investigate the influence of delmopinol hydrochloride on the cell surface morphology of gram-negative and gram-positive bacterial cells by using transmission electron microscopy. A second purpose was to evaluate the extraction of cell wall material caused by delmopinol and the binding of radiolabelled delmopinol to the various strains. Fresh isolates and type strains of gram-negative rods associated with periodontal disease, Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and strains of the gram-positive streptococci Streptococcus sanguis, Streptococcus mutans and Streptococcus salivarius, were exposed to 3.2 mM (0.1%) or 6.4 mM (0.2%) delmopinol hydrochloride from 1 to 90 min. For electron microscopy the cells were fixed and negatively contrast-stained. Treatment with 6.4 mM delmopinol for 1 min resulted in marked ultrastructural changes of cell wall components and the outer cell membrane of the 3 gram-negative species compared with control cells, whereas the gram-positive streptococci treated with delmopinol showed little or no morphologic alteration as compared with untreated cells. The result from the electron microscopy was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins released from bacterial cells treated as for electron microscopy. More material was extracted from the gram-negative rods than from the gram-positive cocci. Significantly more delmopinol bound to the gram-negative rods than to the streptococci. It appears that the amphiphilic properties of delmopinol make gram-negative rods more vulnerable to delmopinol than gram-positive streptococci.