Destructive periodontal diseases are characterized by tissue breakdown partly mediated by various enzymes originating from bacteria and/or tissue. Collagen and fibronectin are two of the main substrates available for enzyme activity. Since chlorhexidine is largely used during and after periodontal therapy, we have investigated the effects of chlorhexidine upon some bacterial proteases. Our data indicate that chlorhexidine inhibits, on a dose-dependent manner, both fibronectin and collagen hydrolysis mediated by either bacteroides (porphyromonas) gingivalis or bacteroides intermedius. Thus, it might be hypothesized that a side from its bactericidal activity, chlorhexidine helps to prevent periodontal tissue destruction directly by enzyme inhibition.