Chlorhexidine is a cationic biguanide with very low water solubil-ity. Water-soluble chlorhexidine digluconate is used in water-based formulations as an antiseptic. It is active against vegetative bacteria and mycobacteria and has moderate activity against fungi and viruses. It strongly adsorbs to bacterial membranes, causing leakage of small molecules and precipitation of cytoplasmic proteins. It is active at pH 5.5–7.0. Chlorhexidine gluconate is slower in its action than alcohols, but, because of its persistence, it has residual activity when used repeatedly, producing bactericidal action equivalent to alcohols. It is most effective against gram-positive cocci and less active against gram-positive and gram-negative rods. Spore germination is inhibited by chlorhexidine. Chlorhexidine digluconate is resistant to inhibition by blood and organic materials. However, anionic and nonionic agents in moisturizers, neutral soaps, and surfactants may neutralize its action. Chlorhexidine digluconate formulations of 4% concentra-tion have slightly greater antibacterial activity than newer 2% formulations. The combination of chlorhexidine gluconate in 70% alcohol, available in some countries including the United States, is the preferred agent for skin antisepsis in many surgical and percutaneous procedures. The advantage of this combination over povidone-iodine may derive from its more rapid action after application, its retained activity after exposure to body fluids, and its persistent activity on the skin. Chlorhexidine has a very low skin-sensitizing or irritating capacity. Oral toxicity is low because it is poorly absorbed from the alimentary tract. Chlorhexidine must not be used during surgery on the middle ear because it causes sensorineural deafness. Similar neural toxicity may be encountered during neurosurgery.