The compounds benzyloxycarbonyl-L-leucyl-hydroxamate (Z-Leu-NHOH), phosphoryl-L-leucyl-L-phenylalanine (P-Leu-Phe) and 2-mercaptoacetyl-L-phenylalanyl-L-leucine (HSAc-Phe-Leu) strongly inhibit the activity of Pseudomonas elastase in vitro. The capacity of these inhibitors to prevent corneal melting and perforation due to the elastase was examined in rabbit eyes by intrastromal injections of elastase solutions containing the various inhibitors. HSAc-Phe-Leu was substantially more effective than the other two inhibitors. It completely prevented corneal perforation, markedly delayed the appearance of melting and kept the degree of melting at a minimum. Subconjunctival injections of HSAc-Phe-Leu given prior to enzyme administration delayed but did not prevent corneal melting or perforation, whereas frequent topical application with drops of this inhibitor completely prevented corneal melting. It is suggested that HSAc-Phe-Leu or similarly structured inhibitors of the elastase might be helpful in the management of corneal infections with Pseudomonas aeruginosa.