Clinical and laboratory studies were carried out to compare the antibacterial properties of two antiseptic mouthwashes, namely 1% povidone iodine and 0.2% chlorhexidine gluconate. In a group of 10 subjects after a single rinse with povidone iodine, an immediate mean fall in total salivary aerobes and anaerobes occurred, followed by a return to normal levels by 1-hour postrinsing. With chlorhexidine gluconate a similar but greater reduction in salivary bacterial counts was observed, which was still present up to the 7-h postrinsing period. Saliva samples obtained from the subjects 2 min after rinsing with providone iodine produced little or no inhibition to the growth of a test organism in vitro, whereas following chlorhexidine gluconate, antibacterial activity was present in the saliva specimens up to the 3-h sampling time. Using culture media containing comparable levels of soluble protein to saliva, the minimum inhibitory concentrations of povidone iodine against several standard test organisms were much higher than those of chlorhexidine gluconate. The results suggest that povidone iodine, as a mouthwash, exerts only an immediate antibacterial effect and unlike chlorhexidine, is not retained at antibacterial levels within the oral cavity after expectoration. This lack of prolonged action of povidone iodine in the oral cavity would appear to be relevant to its reported lack of antiplaque activity.