The aim of the present study was to assess the penetration of chlorhexidine through the oral mucosa. Ten albino guinea pigs had the oral cavity exposed to 0.2 %14C-labelled chlorhexidine for 1 min after initial rinsing with water. Five animals were sacrificed after 30 min and 5 after 60 min. Biopsies from the tongue, palate, gingiva and the buccal mucosa were frozen in liquid nitrogen, cut, fixed and prepared for autoradiography. The surface layers of the epithelium contained the greater part of the labelled material in sections from the tongue, palate and gingiva. Below these heavily labelled surface layers a scattered distribution was noticed throughout the epithelium. Sections from the buccal mucosa showed less surface labelling, but a slight accumulation of label close to the basement membrane was seen. Though labelling was more abundant in the epithelium than in the connective tissue, chlorhexidine had also penetrated into the connective tissue in sections from the buccal mucosa, the gingiva and the ventral side of the tongue.