In an in vivo cat model, wide-field specular microscopy and scanning electron microscopy were used to observe whether heat-denatured sodium hyaluronate causes cell damage to the corneal endothelium. The endothelial cell toxicities of various drugs, including 0.01% benzalkonium chloride, 0.2% chlorhexidine digluconate, and 0.5% lidocaine, mixed with intact or untreated sodium hyaluronate were also investigated. Neither heat-denatured nor intact or untreated sodium hyaluronate alone had any adverse effect on the corneal endothelium in cats, whereas 0.01% benzalkonium chloride and 0.2% chlorhexidine digluconate, mixed with sodium hyaluronate, caused substantial endothelial morphologic changes, which resulted in corneal edema. By comparison, 0.5% lidocaine with sodium hyaluronate was found to have minimal effect on the corneal endothelium in cats. These findings indicate that some chemical contaminant with sodium hyaluronate, not heat-denatured sodium hyaluronate, induces an immediate onset of pseudophakic bullous keratopathy.