A-16686, a new glycoproteide antibiotic from Actinoplanes sp., was evaluated as a potential antiplaque agent in comparison with chlorhexidine, benzalkonium chloride, and cetylpyridinium chloride. A-16686 had good activity against gram-positive organisms associated with dental plaque (various streptococci, Streptococcus mutans in particular, lactobacilli, Actinomyces viscosus, and Actinomyces naeslundii); most of the strains tested were clinical isolates. It was bactericidal for streptococci (MBC/MIC ratio of less than or equal to 8 for 92% of the strains) and for growing cells of S. mutans briefly exposed to antibiotic (99.9% killing within 5 min of contact with 200 micrograms of A-16686 per ml). It also inhibited the in vitro plaque formation by S. mutans and had good activity against preformed plaques. For most cases, its activity was comparable to those of chlorhexidine, benzalkonium chloride, and cetylpyridinium chloride. A-16686 appears to be a promising antiplaque agent because of the following attributes: narrow spectrum of activity, rapid bactericidal action, lack of selection of resistant mutants, absence of cross-resistance with clinically used antibiotics, nonabsorption by oral route, good tolerability by the oral mucosa (rats and dogs), and physical characteristics (white powder, soluble in water).